22.6: Atherosclerosis I: Introduction

Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.

Etiology and risk factors

The cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid infiltration, and inflammatory processes within the arterial wall. Key factors initiating the pathogenesis include:

• Increased blood pressure exerts excessive mechanical stress on the arterial wall.
• Elevated low-density lipoprotein (LDL) cholesterol levels can infiltrate and accumulate within the intima.
• Nicotine in cigarette smoke impairs the function of the endothelium and promotes atherosclerosis by increasing its permeability to lipids and fostering an environment conducive to plaque formation.
• Uncontrolled diabetes is characterized by high blood glucose levels that can damage proteins and lipids, further injuring the endothelium.
• Inflammatory diseases like arthritis contribute to a systemic pro-inflammatory state.

These factors disrupt the endothelial layer's integrity, making it permeable to lipoproteins and initiating plaque formation.

Risk factors for atherosclerosis also include variables that exacerbate the disease's progression or severity, such as advanced age, chronic stress, and family history.

Pathophysiology

The pathophysiology of atherosclerosis involves several key stages and mechanisms:

• Endothelial Dysfunction: This process begins with damage to the endothelium, which makes it permeable to circulating lipoproteins (notably LDL cholesterol).
• Lipid Accumulation: The LDL undergoes oxidation. Oxidized LDL triggers an inflammatory response, attracting macrophages that transform into foam cells. These foam cells accumulate to form fatty streaks, the earliest visible sign of atherosclerosis. Fatty streaks are yellow and smooth and protrude slightly into the lumen of the artery.
• Inflammatory Response: The accumulation of foam cells exacerbates inflammation, attracting more immune cells and releasing cytokines. These cytokines promote the migration and proliferation of smooth muscle cells (SMCs) into the intima, contributing to plaque growth by producing extracellular matrix components like collagen.
• Plaque Progression and Complications: Plaques can grow slowly, obstructing blood flow, or rupture suddenly. A stable plaque restricts blood flow, leading to conditions such as angina, while a ruptured plaque can cause a myocardial infarction or stroke by triggering blood clot formation.
• Calcification and Advanced Lesions: Advanced lesions may undergo calcification, hardening the plaque, reducing arterial elasticity, and increasing the risk of plaque rupture.