{"id":365,"date":"2023-12-04T10:24:32","date_gmt":"2023-12-04T15:24:32","guid":{"rendered":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/chapter\/pathophysiology-of-atherosclerosis-and-angina\/"},"modified":"2023-12-04T10:46:44","modified_gmt":"2023-12-04T15:46:44","slug":"pathophysiology-of-atherosclerosis-and-angina","status":"web-only","type":"chapter","link":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/chapter\/pathophysiology-of-atherosclerosis-and-angina\/","title":{"raw":"Pathophysiology of Atherosclerosis","rendered":"Pathophysiology of Atherosclerosis"},"content":{"raw":"\n<div class=\"textbox textbox--learning-objectives\"><header class=\"textbox__header\">\n<p class=\"textbox__title\">Learning Objectives<\/p>\n\n<\/header>\n<div class=\"textbox__content\">\n\nBy the end of this chapter, you will be able to:\n<ul>\n \t<li>identify and explain the main processes that occur during various stages of atherosclerotic plaque development<\/li>\n \t<li>describe the biological rationale for the most common locations of atherosclerotic plaques<\/li>\n \t<li>describe common clinical scenarios of atherosclerosis progression<\/li>\n<\/ul>\n<\/div>\n<\/div>\n&nbsp;\n\nAtherosclerosis develops as a result of a continuous process that involves endothelial activation, lipid accumulation, atheroma plaque formation, vascular remodeling, and ultimate narrowing of the blood vessel lumen. This blood flow restriction due to atherosclerosis can manifest a variety of clinical diagnoses, which are named based on the location of atherosclerotic plaque (heart attack, stroke, and [pb_glossary id=\"1170\"]peripheral artery disease[\/pb_glossary] )\n\nAtherosclerosis progression is initiated by<strong> endothelial activation<\/strong> in response to cardiovascular risk factors, such as[pb_glossary id=\"1169\"] hypertension[\/pb_glossary], high blood glucose, smoking, increased cholesterol levels, etc.\n<h3>Common locations of atherosclerotic plaques<\/h3>\nEven though the vascular tree is uniformly exposed to metabolic risk factors, <em><strong>some regions are more likely to form atherosclerotic plaques<\/strong><\/em> than others. This phenomenon can be partially explained by mechanical stress (wall shear stress, WSS) and type of blood flow ([pb_glossary id=\"1171\"]laminar[\/pb_glossary] vs [pb_glossary id=\"1172\"]turbulent[\/pb_glossary]), <em><strong>Figure 8.24<\/strong><\/em>.\n\nBlood flow disturbance in branching points and [pb_glossary id=\"1173\"]bifurcation[\/pb_glossary]s of the vascular tree results in a specific distribution of atherosclerotic plaques, with the majority of them forming in these common atheroma-prone regions.\n<div class=\"textbox\">\n\nThis trend highlights the importance of<strong> arterial branches and bifurcations<\/strong> in the diagnosis of atherosclerotic lesions.\n\nSome examples of such locations include the bifurcations of:\n<ul>\n \t<li>abdominal aorta into right and left iliac arteries<\/li>\n \t<li>common carotid arteries into external and internal carotic arteries<\/li>\n \t<li>left coronary artery into left anterior descending (LAD) and circumflex<\/li>\n<\/ul>\n<\/div>\n&nbsp;\n\n&nbsp;\n\n[caption id=\"attachment_3211\" align=\"aligncenter\" width=\"878\"]<img class=\" wp-image-3211\" src=\"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-content\/uploads\/sites\/2131\/2023\/12\/atherosclerotic-aorta-patho-scaled-1.jpg\" alt=\"image of aorta experiencing normal laminar flow vs turbulent flow. Turbulent flow starts the process of atherosclerotic plaque formation\" width=\"878\" height=\"1107\"> <em><strong>Figure 8.24<\/strong><strong> Effects of blood flow and mechanical stress on atherosclerotic plaque formation<\/strong><\/em>.A) Endothelial cells appear flat in straight vessel segments with laminar flow and physiological (moderate) WSS;&nbsp; High-curvature vessel segments (bifurcations and branch points) exhibit turbulent flow, reduced WSS, and cobblestone appearance of endothelial cells. B) Low shear stress promotes endothelial dysfunction and LDL accumulation, initiating atherosclerotic plaque formation in athero-prone regions.&nbsp; &nbsp;Used under CC-BY license form <em>Int. J. Mol. Sci.<\/em>&nbsp;<b>2022<\/b>,&nbsp;<em>23<\/em>(6), 3346;&nbsp;<a href=\"https:\/\/doi.org\/10.3390\/ijms23063346\">https:\/\/doi.org\/10.3390\/ijms23063346<\/a>[\/caption]\n\n<div class=\"textbox shaded\">Atherosclerotic plaque formation starts with the fatty streak (accumulation of lipids within the intima) and progresses into the fibrous plaque with a necrotic core - a complex structure that can facilitate clot formation and\/or detach and become an embolus.<\/div>\n<h2>Stages of atherosclerotic plaque formation<\/h2>\n<ol>\n \t<li><strong><strong><strong><strong>Lesion initiation<\/strong><\/strong><\/strong><\/strong>Atherosclerosis plaque formation begins with activation and\/or damage to the [pb_glossary id=\"794\"]endothelium[\/pb_glossary], which disrupts the normal process of [pb_glossary id=\"1212\"]LDL[\/pb_glossary] intake and metabolism. As a result, LDL is modified and accumulated within the [pb_glossary id=\"1033\"]tunica intima[\/pb_glossary] of a vessel. Endothelial activation\/damage affects its permeability, stimulates [pb_glossary id=\"1198\"]leukocyte[\/pb_glossary] adhesion to its surface, and [pb_glossary id=\"1199\"]diapedesis[\/pb_glossary]. The leukocytes recruited from the blood into the blood vessel wall are [pb_glossary id=\"1174\"]monocyte[\/pb_glossary]s, that become <em><strong>macrophages<\/strong><\/em> once they leave the systemic blood circulation and migrate into tissues.Once within the intimal layer, LDL particles are oxidized by free radicals that are contained in the extracellular matrix and\/or produced by recruited [pb_glossary id=\"1174\"]monocyte[\/pb_glossary]s. <strong>Oxidized LDL<\/strong> (oxLDL) is a <strong>key inflammatory component<\/strong> that facilitates atherosclerosis progression. These initial processes create a \u201cvicious circle\u201d that results in further recruitment of monocytes, LDL retention, and oxLDL accumulation. Recruited monocytes and vascular smooth muscle cells (VSMCs) within the tunica intima engulf oxLDL and become \u201c<strong>foam cells<\/strong>\u201d - a name given to these cells because of a foamy appearance of the cytoplasm due to the oxLDL deposition.<\/li>\n<\/ol>\n[caption id=\"attachment_4903\" align=\"aligncenter\" width=\"3000\"]<img class=\"wp-image-4903 size-full\" src=\"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-content\/uploads\/sites\/2131\/2023\/12\/Vicious-circle.png\" alt=\"the life cycle of a macrophage in the subendothelial space of a vessel. A newly recruited macrophage enters the subendothelial space and releases its free radicals as part of its inflammatory role. These radicals convert LDL to oxidized LDL. The macrophages then engulf the oxidized LDL transforming the macrophage into a fat-laden foam cell. The foam cell then sends inflammatory chemicals which recruit more macrophages to the site and the cycle continues.\" width=\"3000\" height=\"2100\"> <strong>Fig 8.25. Vicious circle of atherosclerosis initiation. <\/strong>Created by Tetiana Povshedna with Biorender.com under the creative commons license[\/caption]\n\n<strong>&nbsp;2. Fatty streak&nbsp;<\/strong>\n\nAs the \u201cvicious circle\u201d progresses, LDL is deposited both inside cells and in the extracellular matrix, and cholesterol crystals form. The initial lesion increases in size and appears as a <em><strong>visible flat yellow streak<\/strong><\/em> on the luminal side of the vessel.\n\n<strong>&nbsp;3. Fibrous plaque<\/strong>\n\nFoam cells (derived from macrophages and [pb_glossary id=\"1175\"] VSMC[\/pb_glossary]s ) undergo cellular death ([pb_glossary id=\"1200\"]apoptosis[\/pb_glossary]) and release their contents within the tunica intima. These contents are further engulfed by macrophages in an attempt to \"clean\" the lesion site. However, an overwhelming amount of oxLDL, dead cells, cholesterol crystals, and extracellular debris form a soft <strong>\"necrotic\" core<\/strong> of growing atherosclerotic plaque. As the lesion progresses, it can accumulate calcium salts and harden over time, impairing the elasticity of blood vessels and their ability to dilate and contract in response to blood pressure fluctuations.\n\nIn response to the atherosclerotic lesion progression, more [pb_glossary id=\"1175\"]VSMC[\/pb_glossary]s are recruited from the [pb_glossary id=\"1034\"]tunica media [\/pb_glossary]to the [pb_glossary id=\"1033\"]intima[\/pb_glossary] to form a <strong>fibrous cap<\/strong> - a protective layer that covers the necrotic core. Normally, VSMCs facilitate contraction\/dilation of blood vessels, but once recruited to tunica intima, they switch towards synthetic activity. VSMCs within the fibrous cap produce a large amount of extracellular matrix (collagen and elastin fibers, proteoglycans) to \"cover\" the soft necrotic core and stabilize the plaque. The fibrous cap prevents plaque rupture and serves as a barrier between the lumen of the vessel and the necrotic core which, if exposed to the blood flow, can trigger the formation of a blood clot.\n\n<strong>&nbsp;4. Outcomes&nbsp;<\/strong>\n\nThe thickness of the fibrous cap covering the soft necrotic core of an atherosclerotic lesion, as well as its composition (the amount of collagen\/elastin fibers), affect the stability of the plaque and clinical outcomes. As atheroma increases in size, inflammation within the plaque (pro-inflammatory cytokines released by macrophages), as well as inflammatory[pb_glossary id=\"1201\"] cytokines[\/pb_glossary] in the bloodstream can affect the vulnerability of the plaque.\n\nAtherosclerotic plaques can become more vulnerable if [pb_glossary id=\"1175\"]VSMC[\/pb_glossary]s within the fibrous cap respond to inflammation by producing enzymes that degrade components of the extracellular matrix, weakening the fibrous cap and making it more susceptible to rupture. A weaker fibrous cap increases the likelihood of the necrotic core getting exposed to the blood flow, which can result in clot formation on top of the plaque.\n\n[caption id=\"attachment_4904\" align=\"aligncenter\" width=\"2560\"]<img class=\"wp-image-4904 size-full\" src=\"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-content\/uploads\/sites\/2131\/2023\/12\/atheroma-formation-scaled-1.jpg\" alt=\"Segments of an artery in developing stages of atherosclerosis are shown, with a lower panel that focusses the tunica intima and tunica media layers. The health artery shows a negligible space in the intima between the endothelial and smooth muscle layers. As the artery progresses to atherosclerosis, more immune cells and lipoproteins begin to fill the intimal space. As the fatty streak develops into a plaque, foam cells form a large plaque with a necrotic core AND smooth muscle cells grow both above and below the plaque. The fibrous atherosclerotic plaque has a cap of smooth muscle cells between the endothelial layer and the necrotic core. When the plaque ruptures, the necrotic core has breached both the smooth muscle and endothelial layers, exposing it to the blood.\" width=\"2560\" height=\"2375\"> <strong>Figure 8.26 - Schematic representation of atheroma plaque formation<\/strong> from a healthy artery to (A) Lesion formation, (B) Fatty streak, (C) Fibrous plaque, and (D) Plaque rupture underlying the most important events that contribute to its development in each stage.[\/caption]\n\n<div class=\"textbox textbox--key-takeaways\"><header class=\"textbox__header\">\n<p class=\"textbox__title\">Key Takeaways<\/p>\n\n<\/header>\n<div class=\"textbox__content\">\n<ol>\n \t<li>Circulating monocytes (macrophages once outside of the bloodstream) play an important role in atherosclerosis initiation and progression and undergo morphological changes in the process<\/li>\n \t<li style=\"font-weight: 400\">Inflammation is relevant at all stages of atherosclerosis, from lesion initiation to its rupture<\/li>\n \t<li style=\"font-weight: 400\">Plaque stability determines the likelihood and severity of clinical complications<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<h2>Main scenarios of the atheroma progression<\/h2>\n<ul>\n \t<li style=\"font-weight: 400\">growth of the plaque, progressive obstruction of the blood vessel lumen;<\/li>\n \t<li style=\"font-weight: 400\">erosion\/rupture of the fibrous cap with subsequent clot formation on its surface;<\/li>\n \t<li style=\"font-weight: 400\">plaque\/clot disruption and formation of the [pb_glossary id=\"1176\"]embolus[\/pb_glossary] in the bloodstream;<\/li>\n \t<li style=\"font-weight: 400\">increased susceptibility to [pb_glossary id=\"1177\"]aneurysm[\/pb_glossary] formation ( Similarly to the process within the fibrous cap, extracellular matrix can be degraded within tunica media of the large vessels, weakening the muscular layer and making it more vulnerable to [pb_glossary id=\"1178\"]dilatation[\/pb_glossary])<\/li>\n<\/ul>\n<div align=\"left\">\n\n[caption id=\"attachment_4905\" align=\"aligncenter\" width=\"1280\"]<img class=\"wp-image-4905 size-full\" src=\"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-content\/uploads\/sites\/2131\/2023\/12\/Late_complications_of_atherosclerosis.png\" alt=\"an artery is split into six segments, with a wall removed to demonstrate the development of an atherosclerotic plaque across the three tunics. The normal vessel demonstrates a smooth red surface. As the artery develops a fatty streak, the cells in the subendothelial layer gets thicker, narrowing the vessel lumen minimally. As the fatty streak develops into a fibrofatty plaque, a thick yellow plaque develops between the endothelial and smooth muscle layer, greatly reducing the vessel luminal opening. The advanced\/vulnerable plaque is then split into three possible consequences: critical stenosis where the yellow fatty plaque takes up almost the entire luminal space; superimposed thrombus where the yellow plaque takes up most of the space, but a blood clot has formed in the luminal space; and Aneurysm and rupture where the blood vessel itself tears at the level of where the small luminal space was still open.\" width=\"1280\" height=\"913\"> <strong>Figure 8.27. Late complications of atherosclerosis.<\/strong> Created by npatchett on Wikimedia, licensed under the Creative Commons Attribution-Share Alike 4.0 International license.[\/caption]\n\n<\/div>\n<h3>Clinical scenarios of atherosclerosis progression<\/h3>\nAs mentioned earlier, the distribution of atheromas within the vascular tree is non-random and most commonly occurs at the branching points and bifurcation of large arteries.\nAs a result, clinical complications of atherosclerosis present as a wide array of symptoms and diagnoses (<em><strong>Figure 8.28<\/strong><\/em>)\n\n[caption id=\"attachment_4906\" align=\"aligncenter\" width=\"3000\"]<img class=\"wp-image-4906 size-full\" src=\"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-content\/uploads\/sites\/2131\/2023\/12\/Untitled-2.png\" alt=\"The major arteries of the body are visible with arrows pointing to common areas of atherosclerotic changes: brain, carotid (neck), thoracic (chest), heart, kidney, abdominal, and peripheral arteries (upper &amp; lower limbs)\" width=\"3000\" height=\"2100\"> <strong>Figure 8.28. Clinical consequences of atherosclerosis<\/strong>. Created by Tetiana Povshedna with Biorender.com, under its creative commons license[\/caption]\n<h1>Section summary<\/h1>\nMicroscopic and macroscopic changes that occur during the atherosclerosis progression are summarized in Fig 8.29.\n\n<em><strong>Fig 8.29&nbsp; Stages of the atherosclerotic plaque formation<\/strong><\/em>\n<div align=\"left\">\n<table class=\"grid aligncenter\" style=\"height: 370px;width: 1690px\"><caption>&nbsp;<\/caption>\n<tbody>\n<tr class=\"shaded\" style=\"height: 108px\">\n<td style=\"height: 108px;width: 167.75px\">\n<h5><strong>Plaque formation stage<\/strong><\/h5>\n<\/td>\n<td style=\"height: 108px;width: 610.283px\">\n<h5><strong>Microscopic changes in the blood vessel wall (histology)<\/strong><\/h5>\n<\/td>\n<td style=\"height: 108px;width: 350.2px\">\n<h5><strong>Outcome<\/strong><\/h5>\n<\/td>\n<td style=\"height: 108px;width: 318.967px\">\n<h5><strong>Macroscopic changes in the blood vessel wall (gross anatomy)<\/strong><\/h5>\n<\/td>\n<\/tr>\n<tr style=\"height: 31px\">\n<td style=\"height: 31px;width: 167.75px\">1. Lesion initiation<\/td>\n<td style=\"height: 31px;width: 610.283px\">Endothelial activation in response to risk factors (hypertension, lipid products, cigarette smoke, etc). Recruited monocytes and intimal VSMCs capture oxLDL and become foam cells<\/td>\n<td style=\"height: 31px;width: 350.2px\">Initial LDL oxidation and infiltration within the intimal layer<\/td>\n<td style=\"height: 31px;width: 318.967px\">-<\/td>\n<\/tr>\n<tr style=\"height: 31px\">\n<td style=\"height: 31px;width: 167.75px\">2. Fatty streak<\/td>\n<td style=\"height: 31px;width: 610.283px\">Recruited monocytes and intimal VSMCs become foam cells; cholesterol crystals form within the intima<\/td>\n<td style=\"height: 31px;width: 350.2px\">Intracellular and extracellular LDL deposition<\/td>\n<td style=\"height: 31px;width: 318.967px\">Bright yellow lesions on the luminal surface of the vessel; minimally raised<\/td>\n<\/tr>\n<tr style=\"height: 107px\">\n<td style=\"height: 107px;width: 167.75px\">3. Fibrous plaque<\/td>\n<td style=\"height: 107px;width: 610.283px\">Foam cells, recruited immune cells, and cholesterol crystals form a soft necrotic core. Impaired clearance of apoptotic cells, increased cellular death, and intraplaque hemorrhages facilitate its expansion.\n\nVSMCs from media are recruited to the intimal layer, secrete collagen-rich extracellular matrix, and form a protective fibrous cap.<\/td>\n<td style=\"height: 107px;width: 350.2px\">Formation of the necrotic core and protective fibrous cap; thickness, composition, and collagen content of the fibrous cap determine stability of the plaque<\/td>\n<td style=\"height: 107px;width: 318.967px\">Firm, visible, raised, homogenous, well-marked white areas on the luminal surface of the vessel; sometimes areas of calcification are present<\/td>\n<\/tr>\n<tr style=\"height: 31px\">\n<td style=\"height: 31px;width: 167.75px\">4.1 Plaque rupture\/erosion<\/td>\n<td style=\"height: 31px;width: 610.283px\">Erosion (loss of endothelium) or rupture (disturbed fibrous cap) expose the thrombogenic core of the plaque and initiate coagulation<\/td>\n<td style=\"height: 31px;width: 350.2px\">Thrombus formation<\/td>\n<td style=\"height: 31px;width: 318.967px\">Heterogeneous raised lesions associated with surface thrombosis<\/td>\n<\/tr>\n<tr style=\"height: 15px\">\n<td style=\"height: 15px;width: 167.75px\">4.2. Plaque growth<\/td>\n<td style=\"height: 15px;width: 610.283px\">Expansion of the necrotic core increases the size of the plaque<\/td>\n<td style=\"height: 15px;width: 350.2px\">Lumen obstruction<\/td>\n<td style=\"height: 15px;width: 318.967px\">Firm lesions that completely close the blood vessel lumen<\/td>\n<\/tr>\n<tr style=\"height: 47px\">\n<td style=\"height: 47px;width: 167.75px\">4.3. Aneurysm formation and rupture<\/td>\n<td style=\"height: 47px;width: 610.283px\">Weakening of the tunica media might appear as fragmentation in the superficial layers (border between tunica media and tunica intima). Muscular layer of the blood vessel wall can appear condensed, the amount of elastic fibers is decreased<\/td>\n<td style=\"height: 47px;width: 350.2px\">Early stages - ballooning of the vessel wall, later stages - rupture<\/td>\n<td style=\"height: 47px;width: 318.967px\">Rupture of the blood vessel (often fatal)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<h1><strong>References<\/strong><\/h1>\nJebari-Benslaiman, S., Galicia-Garc\u00eda, U., Larrea-Sebal, A., Olaetxea, J. R., Alloza, I., Vandenbroeck, K., Benito-Vicente, A., &amp; Mart\u00edn, C. (2022). Pathophysiology of Atherosclerosis. International journal of molecular sciences, 23(6), 3346. <a href=\"https:\/\/doi.org\/10.3390\/ijms23063346\">https:\/\/doi.org\/10.3390\/ijms23063346<\/a>\n\n<a href=\"https:\/\/www.statpearls.com\/ArticleLibrary\/viewarticle\/17943\">https:\/\/www.statpearls.com\/ArticleLibrary\/viewarticle\/17943<\/a>\n<h1>Review questions<\/h1>\n[h5p id=\"195\"]\n","rendered":"<div class=\"textbox textbox--learning-objectives\">\n<header class=\"textbox__header\">\n<p class=\"textbox__title\">Learning Objectives<\/p>\n<\/header>\n<div class=\"textbox__content\">\n<p>By the end of this chapter, you will be able to:<\/p>\n<ul>\n<li>identify and explain the main processes that occur during various stages of atherosclerotic plaque development<\/li>\n<li>describe the biological rationale for the most common locations of atherosclerotic plaques<\/li>\n<li>describe common clinical scenarios of atherosclerosis progression<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<p>&nbsp;<\/p>\n<p>Atherosclerosis develops as a result of a continuous process that involves endothelial activation, lipid accumulation, atheroma plaque formation, vascular remodeling, and ultimate narrowing of the blood vessel lumen. This blood flow restriction due to atherosclerosis can manifest a variety of clinical diagnoses, which are named based on the location of atherosclerotic plaque (heart attack, stroke, and <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1170\">peripheral artery disease<\/a> )<\/p>\n<p>Atherosclerosis progression is initiated by<strong> endothelial activation<\/strong> in response to cardiovascular risk factors, such as<a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1169\"> hypertension<\/a>, high blood glucose, smoking, increased cholesterol levels, etc.<\/p>\n<h3>Common locations of atherosclerotic plaques<\/h3>\n<p>Even though the vascular tree is uniformly exposed to metabolic risk factors, <em><strong>some regions are more likely to form atherosclerotic plaques<\/strong><\/em> than others. This phenomenon can be partially explained by mechanical stress (wall shear stress, WSS) and type of blood flow (<a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1171\">laminar<\/a> vs <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1172\">turbulent<\/a>), <em><strong>Figure 8.24<\/strong><\/em>.<\/p>\n<p>Blood flow disturbance in branching points and <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1173\">bifurcation<\/a>s of the vascular tree results in a specific distribution of atherosclerotic plaques, with the majority of them forming in these common atheroma-prone regions.<\/p>\n<div class=\"textbox\">\n<p>This trend highlights the importance of<strong> arterial branches and bifurcations<\/strong> in the diagnosis of atherosclerotic lesions.<\/p>\n<p>Some examples of such locations include the bifurcations of:<\/p>\n<ul>\n<li>abdominal aorta into right and left iliac arteries<\/li>\n<li>common carotid arteries into external and internal carotic arteries<\/li>\n<li>left coronary artery into left anterior descending (LAD) and circumflex<\/li>\n<\/ul>\n<\/div>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<figure id=\"attachment_3211\" aria-describedby=\"caption-attachment-3211\" style=\"width: 878px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-3211\" src=\"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-content\/uploads\/sites\/2131\/2023\/12\/atherosclerotic-aorta-patho-scaled-1.jpg\" alt=\"image of aorta experiencing normal laminar flow vs turbulent flow. Turbulent flow starts the process of atherosclerotic plaque formation\" width=\"878\" height=\"1107\" \/><figcaption id=\"caption-attachment-3211\" class=\"wp-caption-text\"><em><strong>Figure 8.24<\/strong><strong> Effects of blood flow and mechanical stress on atherosclerotic plaque formation<\/strong><\/em>.A) Endothelial cells appear flat in straight vessel segments with laminar flow and physiological (moderate) WSS;&nbsp; High-curvature vessel segments (bifurcations and branch points) exhibit turbulent flow, reduced WSS, and cobblestone appearance of endothelial cells. B) Low shear stress promotes endothelial dysfunction and LDL accumulation, initiating atherosclerotic plaque formation in athero-prone regions.&nbsp; &nbsp;Used under CC-BY license form <em>Int. J. Mol. Sci.<\/em>&nbsp;<b>2022<\/b>,&nbsp;<em>23<\/em>(6), 3346;&nbsp;<a href=\"https:\/\/doi.org\/10.3390\/ijms23063346\">https:\/\/doi.org\/10.3390\/ijms23063346<\/a><\/figcaption><\/figure>\n<div class=\"textbox shaded\">Atherosclerotic plaque formation starts with the fatty streak (accumulation of lipids within the intima) and progresses into the fibrous plaque with a necrotic core &#8211; a complex structure that can facilitate clot formation and\/or detach and become an embolus.<\/div>\n<h2>Stages of atherosclerotic plaque formation<\/h2>\n<ol>\n<li><strong><strong><strong><strong>Lesion initiation<\/strong><\/strong><\/strong><\/strong>Atherosclerosis plaque formation begins with activation and\/or damage to the <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_794\">endothelium<\/a>, which disrupts the normal process of <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1212\">LDL<\/a> intake and metabolism. As a result, LDL is modified and accumulated within the <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1033\">tunica intima<\/a> of a vessel. Endothelial activation\/damage affects its permeability, stimulates <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1198\">leukocyte<\/a> adhesion to its surface, and <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1199\">diapedesis<\/a>. The leukocytes recruited from the blood into the blood vessel wall are <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1174\">monocyte<\/a>s, that become <em><strong>macrophages<\/strong><\/em> once they leave the systemic blood circulation and migrate into tissues.Once within the intimal layer, LDL particles are oxidized by free radicals that are contained in the extracellular matrix and\/or produced by recruited <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1174\">monocyte<\/a>s. <strong>Oxidized LDL<\/strong> (oxLDL) is a <strong>key inflammatory component<\/strong> that facilitates atherosclerosis progression. These initial processes create a \u201cvicious circle\u201d that results in further recruitment of monocytes, LDL retention, and oxLDL accumulation. Recruited monocytes and vascular smooth muscle cells (VSMCs) within the tunica intima engulf oxLDL and become \u201c<strong>foam cells<\/strong>\u201d &#8211; a name given to these cells because of a foamy appearance of the cytoplasm due to the oxLDL deposition.<\/li>\n<\/ol>\n<figure id=\"attachment_4903\" aria-describedby=\"caption-attachment-4903\" style=\"width: 3000px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4903 size-full\" src=\"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-content\/uploads\/sites\/2131\/2023\/12\/Vicious-circle.png\" alt=\"the life cycle of a macrophage in the subendothelial space of a vessel. A newly recruited macrophage enters the subendothelial space and releases its free radicals as part of its inflammatory role. These radicals convert LDL to oxidized LDL. The macrophages then engulf the oxidized LDL transforming the macrophage into a fat-laden foam cell. The foam cell then sends inflammatory chemicals which recruit more macrophages to the site and the cycle continues.\" width=\"3000\" height=\"2100\" \/><figcaption id=\"caption-attachment-4903\" class=\"wp-caption-text\"><strong>Fig 8.25. Vicious circle of atherosclerosis initiation. <\/strong>Created by Tetiana Povshedna with Biorender.com under the creative commons license<\/figcaption><\/figure>\n<p><strong>&nbsp;2. Fatty streak&nbsp;<\/strong><\/p>\n<p>As the \u201cvicious circle\u201d progresses, LDL is deposited both inside cells and in the extracellular matrix, and cholesterol crystals form. The initial lesion increases in size and appears as a <em><strong>visible flat yellow streak<\/strong><\/em> on the luminal side of the vessel.<\/p>\n<p><strong>&nbsp;3. Fibrous plaque<\/strong><\/p>\n<p>Foam cells (derived from macrophages and <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1175\"> VSMC<\/a>s ) undergo cellular death (<a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1200\">apoptosis<\/a>) and release their contents within the tunica intima. These contents are further engulfed by macrophages in an attempt to &#8220;clean&#8221; the lesion site. However, an overwhelming amount of oxLDL, dead cells, cholesterol crystals, and extracellular debris form a soft <strong>&#8220;necrotic&#8221; core<\/strong> of growing atherosclerotic plaque. As the lesion progresses, it can accumulate calcium salts and harden over time, impairing the elasticity of blood vessels and their ability to dilate and contract in response to blood pressure fluctuations.<\/p>\n<p>In response to the atherosclerotic lesion progression, more <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1175\">VSMC<\/a>s are recruited from the <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1034\">tunica media <\/a>to the <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1033\">intima<\/a> to form a <strong>fibrous cap<\/strong> &#8211; a protective layer that covers the necrotic core. Normally, VSMCs facilitate contraction\/dilation of blood vessels, but once recruited to tunica intima, they switch towards synthetic activity. VSMCs within the fibrous cap produce a large amount of extracellular matrix (collagen and elastin fibers, proteoglycans) to &#8220;cover&#8221; the soft necrotic core and stabilize the plaque. The fibrous cap prevents plaque rupture and serves as a barrier between the lumen of the vessel and the necrotic core which, if exposed to the blood flow, can trigger the formation of a blood clot.<\/p>\n<p><strong>&nbsp;4. Outcomes&nbsp;<\/strong><\/p>\n<p>The thickness of the fibrous cap covering the soft necrotic core of an atherosclerotic lesion, as well as its composition (the amount of collagen\/elastin fibers), affect the stability of the plaque and clinical outcomes. As atheroma increases in size, inflammation within the plaque (pro-inflammatory cytokines released by macrophages), as well as inflammatory<a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1201\"> cytokines<\/a> in the bloodstream can affect the vulnerability of the plaque.<\/p>\n<p>Atherosclerotic plaques can become more vulnerable if <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1175\">VSMC<\/a>s within the fibrous cap respond to inflammation by producing enzymes that degrade components of the extracellular matrix, weakening the fibrous cap and making it more susceptible to rupture. A weaker fibrous cap increases the likelihood of the necrotic core getting exposed to the blood flow, which can result in clot formation on top of the plaque.<\/p>\n<figure id=\"attachment_4904\" aria-describedby=\"caption-attachment-4904\" style=\"width: 2560px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4904 size-full\" src=\"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-content\/uploads\/sites\/2131\/2023\/12\/atheroma-formation-scaled-1.jpg\" alt=\"Segments of an artery in developing stages of atherosclerosis are shown, with a lower panel that focusses the tunica intima and tunica media layers. The health artery shows a negligible space in the intima between the endothelial and smooth muscle layers. As the artery progresses to atherosclerosis, more immune cells and lipoproteins begin to fill the intimal space. As the fatty streak develops into a plaque, foam cells form a large plaque with a necrotic core AND smooth muscle cells grow both above and below the plaque. The fibrous atherosclerotic plaque has a cap of smooth muscle cells between the endothelial layer and the necrotic core. When the plaque ruptures, the necrotic core has breached both the smooth muscle and endothelial layers, exposing it to the blood.\" width=\"2560\" height=\"2375\" \/><figcaption id=\"caption-attachment-4904\" class=\"wp-caption-text\"><strong>Figure 8.26 &#8211; Schematic representation of atheroma plaque formation<\/strong> from a healthy artery to (A) Lesion formation, (B) Fatty streak, (C) Fibrous plaque, and (D) Plaque rupture underlying the most important events that contribute to its development in each stage.<\/figcaption><\/figure>\n<div class=\"textbox textbox--key-takeaways\">\n<header class=\"textbox__header\">\n<p class=\"textbox__title\">Key Takeaways<\/p>\n<\/header>\n<div class=\"textbox__content\">\n<ol>\n<li>Circulating monocytes (macrophages once outside of the bloodstream) play an important role in atherosclerosis initiation and progression and undergo morphological changes in the process<\/li>\n<li style=\"font-weight: 400\">Inflammation is relevant at all stages of atherosclerosis, from lesion initiation to its rupture<\/li>\n<li style=\"font-weight: 400\">Plaque stability determines the likelihood and severity of clinical complications<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<h2>Main scenarios of the atheroma progression<\/h2>\n<ul>\n<li style=\"font-weight: 400\">growth of the plaque, progressive obstruction of the blood vessel lumen;<\/li>\n<li style=\"font-weight: 400\">erosion\/rupture of the fibrous cap with subsequent clot formation on its surface;<\/li>\n<li style=\"font-weight: 400\">plaque\/clot disruption and formation of the <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1176\">embolus<\/a> in the bloodstream;<\/li>\n<li style=\"font-weight: 400\">increased susceptibility to <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1177\">aneurysm<\/a> formation ( Similarly to the process within the fibrous cap, extracellular matrix can be degraded within tunica media of the large vessels, weakening the muscular layer and making it more vulnerable to <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_365_1178\">dilatation<\/a>)<\/li>\n<\/ul>\n<div style=\"text-align: left;\">\n<figure id=\"attachment_4905\" aria-describedby=\"caption-attachment-4905\" style=\"width: 1280px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4905 size-full\" src=\"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-content\/uploads\/sites\/2131\/2023\/12\/Late_complications_of_atherosclerosis.png\" alt=\"an artery is split into six segments, with a wall removed to demonstrate the development of an atherosclerotic plaque across the three tunics. The normal vessel demonstrates a smooth red surface. As the artery develops a fatty streak, the cells in the subendothelial layer gets thicker, narrowing the vessel lumen minimally. As the fatty streak develops into a fibrofatty plaque, a thick yellow plaque develops between the endothelial and smooth muscle layer, greatly reducing the vessel luminal opening. The advanced\/vulnerable plaque is then split into three possible consequences: critical stenosis where the yellow fatty plaque takes up almost the entire luminal space; superimposed thrombus where the yellow plaque takes up most of the space, but a blood clot has formed in the luminal space; and Aneurysm and rupture where the blood vessel itself tears at the level of where the small luminal space was still open.\" width=\"1280\" height=\"913\" \/><figcaption id=\"caption-attachment-4905\" class=\"wp-caption-text\"><strong>Figure 8.27. Late complications of atherosclerosis.<\/strong> Created by npatchett on Wikimedia, licensed under the Creative Commons Attribution-Share Alike 4.0 International license.<\/figcaption><\/figure>\n<\/div>\n<h3>Clinical scenarios of atherosclerosis progression<\/h3>\n<p>As mentioned earlier, the distribution of atheromas within the vascular tree is non-random and most commonly occurs at the branching points and bifurcation of large arteries.<br \/>\nAs a result, clinical complications of atherosclerosis present as a wide array of symptoms and diagnoses (<em><strong>Figure 8.28<\/strong><\/em>)<\/p>\n<figure id=\"attachment_4906\" aria-describedby=\"caption-attachment-4906\" style=\"width: 3000px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-4906 size-full\" src=\"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-content\/uploads\/sites\/2131\/2023\/12\/Untitled-2.png\" alt=\"The major arteries of the body are visible with arrows pointing to common areas of atherosclerotic changes: brain, carotid (neck), thoracic (chest), heart, kidney, abdominal, and peripheral arteries (upper &amp; lower limbs)\" width=\"3000\" height=\"2100\" \/><figcaption id=\"caption-attachment-4906\" class=\"wp-caption-text\"><strong>Figure 8.28. Clinical consequences of atherosclerosis<\/strong>. Created by Tetiana Povshedna with Biorender.com, under its creative commons license<\/figcaption><\/figure>\n<h1>Section summary<\/h1>\n<p>Microscopic and macroscopic changes that occur during the atherosclerosis progression are summarized in Fig 8.29.<\/p>\n<p><em><strong>Fig 8.29&nbsp; Stages of the atherosclerotic plaque formation<\/strong><\/em><\/p>\n<div style=\"text-align: left;\">\n<table class=\"grid aligncenter\" style=\"height: 370px;width: 1690px\">\n<caption>&nbsp;<\/caption>\n<tbody>\n<tr class=\"shaded\" style=\"height: 108px\">\n<td style=\"height: 108px;width: 167.75px\">\n<h5><strong>Plaque formation stage<\/strong><\/h5>\n<\/td>\n<td style=\"height: 108px;width: 610.283px\">\n<h5><strong>Microscopic changes in the blood vessel wall (histology)<\/strong><\/h5>\n<\/td>\n<td style=\"height: 108px;width: 350.2px\">\n<h5><strong>Outcome<\/strong><\/h5>\n<\/td>\n<td style=\"height: 108px;width: 318.967px\">\n<h5><strong>Macroscopic changes in the blood vessel wall (gross anatomy)<\/strong><\/h5>\n<\/td>\n<\/tr>\n<tr style=\"height: 31px\">\n<td style=\"height: 31px;width: 167.75px\">1. Lesion initiation<\/td>\n<td style=\"height: 31px;width: 610.283px\">Endothelial activation in response to risk factors (hypertension, lipid products, cigarette smoke, etc). Recruited monocytes and intimal VSMCs capture oxLDL and become foam cells<\/td>\n<td style=\"height: 31px;width: 350.2px\">Initial LDL oxidation and infiltration within the intimal layer<\/td>\n<td style=\"height: 31px;width: 318.967px\">&#8211;<\/td>\n<\/tr>\n<tr style=\"height: 31px\">\n<td style=\"height: 31px;width: 167.75px\">2. Fatty streak<\/td>\n<td style=\"height: 31px;width: 610.283px\">Recruited monocytes and intimal VSMCs become foam cells; cholesterol crystals form within the intima<\/td>\n<td style=\"height: 31px;width: 350.2px\">Intracellular and extracellular LDL deposition<\/td>\n<td style=\"height: 31px;width: 318.967px\">Bright yellow lesions on the luminal surface of the vessel; minimally raised<\/td>\n<\/tr>\n<tr style=\"height: 107px\">\n<td style=\"height: 107px;width: 167.75px\">3. Fibrous plaque<\/td>\n<td style=\"height: 107px;width: 610.283px\">Foam cells, recruited immune cells, and cholesterol crystals form a soft necrotic core. Impaired clearance of apoptotic cells, increased cellular death, and intraplaque hemorrhages facilitate its expansion.<\/p>\n<p>VSMCs from media are recruited to the intimal layer, secrete collagen-rich extracellular matrix, and form a protective fibrous cap.<\/td>\n<td style=\"height: 107px;width: 350.2px\">Formation of the necrotic core and protective fibrous cap; thickness, composition, and collagen content of the fibrous cap determine stability of the plaque<\/td>\n<td style=\"height: 107px;width: 318.967px\">Firm, visible, raised, homogenous, well-marked white areas on the luminal surface of the vessel; sometimes areas of calcification are present<\/td>\n<\/tr>\n<tr style=\"height: 31px\">\n<td style=\"height: 31px;width: 167.75px\">4.1 Plaque rupture\/erosion<\/td>\n<td style=\"height: 31px;width: 610.283px\">Erosion (loss of endothelium) or rupture (disturbed fibrous cap) expose the thrombogenic core of the plaque and initiate coagulation<\/td>\n<td style=\"height: 31px;width: 350.2px\">Thrombus formation<\/td>\n<td style=\"height: 31px;width: 318.967px\">Heterogeneous raised lesions associated with surface thrombosis<\/td>\n<\/tr>\n<tr style=\"height: 15px\">\n<td style=\"height: 15px;width: 167.75px\">4.2. Plaque growth<\/td>\n<td style=\"height: 15px;width: 610.283px\">Expansion of the necrotic core increases the size of the plaque<\/td>\n<td style=\"height: 15px;width: 350.2px\">Lumen obstruction<\/td>\n<td style=\"height: 15px;width: 318.967px\">Firm lesions that completely close the blood vessel lumen<\/td>\n<\/tr>\n<tr style=\"height: 47px\">\n<td style=\"height: 47px;width: 167.75px\">4.3. Aneurysm formation and rupture<\/td>\n<td style=\"height: 47px;width: 610.283px\">Weakening of the tunica media might appear as fragmentation in the superficial layers (border between tunica media and tunica intima). Muscular layer of the blood vessel wall can appear condensed, the amount of elastic fibers is decreased<\/td>\n<td style=\"height: 47px;width: 350.2px\">Early stages &#8211; ballooning of the vessel wall, later stages &#8211; rupture<\/td>\n<td style=\"height: 47px;width: 318.967px\">Rupture of the blood vessel (often fatal)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<h1><strong>References<\/strong><\/h1>\n<p>Jebari-Benslaiman, S., Galicia-Garc\u00eda, U., Larrea-Sebal, A., Olaetxea, J. R., Alloza, I., Vandenbroeck, K., Benito-Vicente, A., &amp; Mart\u00edn, C. (2022). Pathophysiology of Atherosclerosis. International journal of molecular sciences, 23(6), 3346. <a href=\"https:\/\/doi.org\/10.3390\/ijms23063346\">https:\/\/doi.org\/10.3390\/ijms23063346<\/a><\/p>\n<p><a href=\"https:\/\/www.statpearls.com\/ArticleLibrary\/viewarticle\/17943\">https:\/\/www.statpearls.com\/ArticleLibrary\/viewarticle\/17943<\/a><\/p>\n<h1>Review questions<\/h1>\n<div class=\"glossary\"><span class=\"screen-reader-text\" id=\"definition\">definition<\/span><template id=\"term_365_1170\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1170\"><div tabindex=\"-1\"><p>the narrowing or blockage of arteries that supply upper\/lower limbs<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1169\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1169\"><div tabindex=\"-1\"><p>elevated blood pressure<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1171\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1171\"><div tabindex=\"-1\"><p>type of fluid flow in which fluid travels smoothly <\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1172\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1172\"><div tabindex=\"-1\"><p>type of fluid flow in which fluid undergoes irregular fluctuations and mixing<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1173\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1173\"><div tabindex=\"-1\"><p>part of the blood vessel where it splits in 2 branches<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_794\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_794\"><div tabindex=\"-1\"><p>Tissue that lines vessels of the lymphatic and cardiovascular system, made up of a simple squamous epithelium.<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1212\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1212\"><div tabindex=\"-1\"><p>low-density lipoprotein, \"bad cholesterol\" , the form that carries lipids from the liver to various body tissue; increased levels of LDL can accumulate within the blood vessel wall and cause atherosclerosis<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1033\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1033\"><div tabindex=\"-1\"><p>(also, tunica interna) innermost lining or tunic of a vessel<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1198\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1198\"><div tabindex=\"-1\"><p>cellular component of blood, also known as white blood cells; part of the immune system<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1199\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1199\"><div tabindex=\"-1\"><p>movement of blood cells through the blood vessel wall<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1174\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1174\"><div tabindex=\"-1\"><p>a type of white blood cell that can further differentiate in macrophages and is involved in adaptive immunity and inflammation<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1175\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1175\"><div tabindex=\"-1\"><p>vascular smooth muscle cells<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1200\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1200\"><div tabindex=\"-1\"><p>\"programmed\" cells death that eliminates abnormal cells <\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1034\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1034\"><div tabindex=\"-1\"><p>middle layer or tunic of a vessel (except capillaries)<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1201\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1201\"><div tabindex=\"-1\"><p>small proteins released by cells; allow for communication between the cells involved in the same type of immune response\/reaction<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1176\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1176\"><div tabindex=\"-1\"><p>unattached mass that travels through the bloodstream and can create blockages, resulting in acute vascular events <\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1177\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1177\"><div tabindex=\"-1\"><p>abnormal ballooning\/ widening of the blood vessel wall cause by it's weakness. Aneurysm rupture is very dangerous and often fatal<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_365_1178\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_365_1178\"><div tabindex=\"-1\"><p>widening<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><\/div>","protected":false},"author":103,"menu_order":14,"template":"","meta":{"pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":["tetiana-p"],"pb_section_license":""},"chapter-type":[],"contributor":[178],"license":[],"class_list":["post-365","chapter","type-chapter","status-web-only","hentry","contributor-tetiana-p"],"part":306,"_links":{"self":[{"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/chapters\/365","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/wp\/v2\/users\/103"}],"version-history":[{"count":1,"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/chapters\/365\/revisions"}],"predecessor-version":[{"id":1281,"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/chapters\/365\/revisions\/1281"}],"part":[{"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/parts\/306"}],"metadata":[{"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/chapters\/365\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/wp\/v2\/media?parent=365"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/chapter-type?post=365"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/wp\/v2\/contributor?post=365"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/wp\/v2\/license?post=365"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}