Atherosclerosis and Coronary Artery Diseases

Atherosclerosis

• Atherosclerosis is a chronic inflammatory process triggered by the accumulation of cholesterol-containing low-density lipoprotein (LDL) particles in the arterial wall.

Risk Factors for Atherosclerosis

• Advanced age
• Male gender
• Smoking
• Dyslipidemia
• Diabetes Mellitus
• Hypertension
• Excess Adiposity and Metabolic Syndrome
• Psychosocial factors
• Low consumption of fruits and vegetables
• Lack of regular physical activity

Genetic of Coronary Atherosclerosis

• Genome Wide Associated Study (GWAS) identified 9p21 as a risk locus
• Felix Jacob Marchand, a German pathologist, discovered the significance of cholesterol in atherosclerosis pathogenesis
• Nikolay Nikolayevich Anichkov, a Russian pathologist, contributed to the understanding of atherosclerosis

Basic Mechanism of Atherosclerosis

• Infiltration of apolipoprotein B (apoB)-containing LDL in the arterial wall
• Turbulent flow leads to increased concentrations of plasma LDL adjacent to the luminal surface
• LDL is retained by proteoglycans and can be modified by oxidation, leading to inflammatory reactions
• Endothelial dysfunction causes increased influx of cholesterol-containing lipoproteins into the arterial intima

Uptake Modification

• Retained LDL is modified by oxidation, serving as an initiating stimulus for inflammatory reactions
• Modified LDL is recognized as a danger-associated molecular pattern (DAMP)

Endothelial Adhesion Molecules and Leukocyte Adhesion and Recruitment

• Oxidized LDL (oxLDL) stimulates endothelial cells to express adhesion molecules
• Leukocytes are recruited to the developing atherosclerotic lesion, producing inflammatory mediators that amplify the inflammatory reaction

Monocyte to Macrophage Differentiation

• Monocytes differentiate into tissue macrophages under the influence of monocyte-colony stimulating factor (M-CSF)
• Macrophages further enrich the proinflammatory milieu, sustaining inflammatory responses and resulting in tissue damage

oxLDL Uptake and Foam Cell Formation

• Oxidized and modified forms of LDL particles bind to scavenger receptors on resident macrophages
• Uptake of lipoprotein particles induces the conversion of macrophages into foam cells, characteristic of the atherosclerotic lesion

Antigen Presentation and Adaptive Immune Response

• Internalization of oxLDL by macrophages and dendritic cells leads to antigen presentation and activation of CD4+ T cells
• Effector CD4+ T cells differentiate into helper T cells (Th cells), which promote macrophage activation and inflammation
• Regulatory T cells (Treg cells) inhibit immune responses and inflammation, acting as atheroprotective factors
• Th17 cells promote fibrosis and enhance lesion stability

Macrophages Apoptosis and Necrotic Core Formation

• Macrophage death through apoptosis leads to defective clearance of lipid-laden apoptotic macrophages
• Defective clearance creates a lipid necrotic core, contributing to atherosclerotic lesion development