Atherosclerosis and Atheromas

Definitions of Atherosclerosis and Atheroma:

• Atherosclerosis specifically refers to the development of atheromas or atherosclerotic plaques within arterial walls.

Composition of Plaques:

• Mostly fat deposits.
• Contains calcium (dystrophic calcification in damaged tissue).
• May include fibrin, thrombus material, cellular debris, red and white blood cells.
• These components cluster together, creating a mass or plaque.

Most Susceptible Vessels:

• Large arteries, including:
  • Aorta
  • Iliac arteries
  • Coronary arteries (heart)
  • Carotid arteries (brain)
• Points of bifurcation:
  • Where a vessel forks or splits into two branches, causing turbulence and shear stress.
  • Turbulence damages vessel walls, favoring plaque formation at these sites.

Impact of plaques:

• Reduced blood flow leads to impaired muscle activity and nerve function.
• Causes ischemia—tissue damage due to lack of oxygen.
• Precipitated by damage to vessel walls at bifurcations.

Risk Factors & Lifestyle:

• Diet: Fat, salt, and cholesterol intake.
• Exercise: Sedentary lifestyles increase risk.
• Stress: Chronic stress contributes to endothelial damage.
• Nature of damage: Daily stress and chronic stress accelerate plaque formation.

Medical Interventions:

• Endarterectomy: Surgical removal of plaques from blood vessel walls, often at bifurcations like the carotids.

Visuals:

• Normal aorta: Smooth, unblocked, laminar blood flow.
• Atherosclerotic aorta: Plaque buildup, causing irregularities and turbulence, which further damages vessel walls and promotes plaque growth.
• Downstream damage: Turbulence propagates stress and injury to smaller arteries downstream.

Lipids and Lipoproteins in Atherosclerosis

Sources of Lipids:

• LDL (Low-Density Lipoprotein):
  • Produced by the liver to transport lipids (mainly cholesterol and triglycerides) to cells.
  • Essential because lipid is an energy source and a building block for cell membranes and hormones.
  • However, LDL particles are “sloppy”, meaning their lipid cargo can accumulate in blood vessel walls, forming atheromas.

Lipoprotein Functions:

• HDL (High-Density Lipoprotein):
  • Known as the scavenger lipoprotein.
  • Collects excess cholesterol and lipids coming from LDL.
  • Returns these lipids to the liver for metabolism, energy production, or bile formation for excretion.

Lipid Metabolism Pathway, HDLs and LDLs:

• Dietary fats:
  • Cholesterol and triglycerides are ingested with food.
  • The intestine breaks down fats into smaller molecules, which are absorbed into the bloodstream.
• Transport:
  • Lipids are water-insoluble, so they are packed into vesicles called lipoproteins with proteins for transport.
  • These vesicles travel to tissues like skeletal muscle (active, needing energy) and adipose tissue (storage, insulation, cushioning).
• Liver processing:
  • Lipids reaching the liver are packaged as LDL—“sloppy” and rich in lipids (~75% lipid content).
  • LDL particles bind to LDL receptors on endothelial and smooth muscle cells lining blood vessels.
  • Excess LDL uptake in vessel walls leads to lipid accumulation and formation of atherosclerotic plaques.

Role of HDL:

• Acts as scavenger: retrieves excess lipids from blood vessel walls.
• Returns lipids to the liver for breakdown and excretion.

Visual Summary (Pie Charts):

• HDL (High-density lipoprotein): ~50% protein, ~50% lipid (cholesterol, triglycerides, phospholipids).
• LDL (Low-density lipoprotein): >75% lipid content, very “sloppy” and prone to depositing lipids in vessel walls.

Pathogenesis of Atherosclerosis:

1. Initial Step: Endothelial injury—damage to the innermost layer (tunica intima) of blood vessels.
   • Causes of damage:
     • Hypertension: Elevated pressure damages vessel walls.
     • Smoking: Damages endothelial cells, increases oxidative stress.
     • Hyperlipidemia: Excess lipids infiltrate the damaged endothelium.
     • Genetic factors: Increased lipid production or receptor activity.
     • Other factors: High homocysteine, turbulent flow at bifurcations, toxins, infections, immune reactions, virus-induced damage.
2. Inflammation Response:
   • Increased C-reactive protein (CRP) as a marker of inflammation.
   • Attraction of white blood cells: monocytes and macrophages.
   • Macrophages ingest lipids and become foamy macrophages (foam cells).
3. Plaque Formation:
4. • Lipids embed into the damaged endothelial space.
   • Platelets adhere, activate, and form a thrombus.
   • Smooth muscle proliferation and fibroblast activity lead to collagen deposition, forming a fibrous cap over the plaque.
   • Plaque can calcify, making it more rigid, less elastic, and prone to fissures or rupture.
5. Progression:
   • Plaques grow larger, narrowing the lumen.
   • Leukocyte, platelet, and lipid accumulation worsen the obstruction.
   • Turbulence from plaque causes further endothelial injury downstream, creating a vicious cycle.
6. Consequences of Plaque Development:

• Reduced blood flow causes ischemia.
• Plates and thrombi can embolize, leading to downstream blockages.
• Plaque rupture can trigger acute events like heart attack or stroke.

Risk Factors:

• Smoking:
  • Decreases HDL (“good” cholesterol), increases LDL (“bad” cholesterol).
  • Promotes vasoconstriction and platelet adhesion, increasing clot risk.
  • Raises heart rate and blood pressure.
• Diabetes:
  • Elevates glucose and lipid levels, damaging endothelium, promoting plaques.
• Hypertension:
  • Causes endothelial injury, accelerating plaque formation.
• Combination factors:
  • Use of birth control pills combined with smoking especially after age 35 greatly increases clotting risk.

Summary:

Atherosclerosis involves fatty deposits causing vessel narrowing and turbulence, leading to progressive damage and risk of infarction.

Large arteries such as the aorta and coronary arteries are particularly vulnerable, and lifestyle factors heavily influence plaque development.

Key Concepts:

• LDL: Delivers lipids but can promote plaque buildup if levels are high.
• HDL: Protects against atherosclerosis by cleaning up excess lipids.
• Managing lipid levels through diet, activity, and medications helps prevent or slow the progression of atherosclerosis.

Atherosclerosis begins with endothelial injury and progression involves lipid accumulation, inflammation, and plaque formation.

Lifestyle factors like smoking, diet, and inactivity significantly influence disease progression, while medical interventions aim to prevent or remove plaques and reduce the risk of acute cardiovascular events.

Surgical removal of plaques is possible, but prevention remains key.