What is the pathophysiological basis for the formation of atherosclerotic plaques in coronary arteries, and how does this process contribute to the development of coronary artery disease (CAD)?
Atherosclerosis is a chronic disease that affects the innermost layer of the endothelium of the large and medium-sized arteries. It is characterized by the accumulation of fats, cholesterol, calcium and other substances on the arterial walls, forming plaques that narrow and stiffen the vessels. Atherosclerosis is a major cause of cardiovascular morbidity and mortality, as it can lead to ischemia, thrombosis and embolism of vital organs such as the heart and brain.
The pathophysiology of atherosclerosis involves a complex interplay of genetic, environmental and behavioral factors that modulate the inflammatory response of the arterial wall to various insults. The main steps in the development of atherosclerotic plaques are:
– Endothelial dysfunction: The endothelium is the inner lining of the blood vessels that regulates vascular tone, permeability, coagulation and inflammation. Endothelial dysfunction is the initial event in atherosclerosis, triggered by risk factors such as hypertension, hyperlipidemia, diabetes, smoking and oxidative stress. These factors impair the production of nitric oxide (NO), a vasodilator and anti-inflammatory molecule, and increase the expression of adhesion molecules, cytokines and chemokines that attract inflammatory cells to the vessel wall.
– Monocyte adhesion and migration: Monocytes are white blood cells that circulate in the blood and respond to inflammatory signals. They adhere to the activated endothelium and migrate into the intima, the innermost layer of the arterial wall. There they differentiate into macrophages, which engulf oxidized low-density lipoprotein (LDL) particles that have leaked from the blood into the intima. Oxidized LDL is a highly pro-inflammatory and cytotoxic form of cholesterol that contributes to endothelial damage and plaque formation.
– Foam cell formation and fatty streak: Macrophages that ingest oxidized LDL become foam cells, which are lipid-laden cells that accumulate in the intima and form fatty streaks. Fatty streaks are the earliest visible lesions of atherosclerosis and can be detected in childhood. They are reversible at this stage, but can progress to more advanced lesions if the inflammatory process persists.
– Smooth muscle cell proliferation and migration: Smooth muscle cells (SMCs) are normally present in the media, the middle layer of the arterial wall that provides structural support and elasticity. Under the influence of growth factors and cytokines released by macrophages and endothelial cells, SMCs proliferate and migrate from the media to the intima, where they secrete extracellular matrix (ECM) components such as collagen and elastin. These components form a fibrous cap that covers and stabilizes the fatty core of the plaque.
– Plaque growth and rupture: As the plaque grows in size and complexity, it encroaches on the lumen of the artery and reduces blood flow to the downstream tissues. This can cause symptoms such as angina (chest pain) or claudication (leg pain) during exertion. However, some plaques remain asymptomatic until they rupture, which is a catastrophic event that exposes the thrombogenic material in the core to the blood stream. This triggers platelet aggregation and clot formation, which can occlude the artery completely or break off and travel to other organs. Depending on the location and extent of occlusion, plaque rupture can result in acute coronary syndrome (ACS), stroke or peripheral arterial disease (PAD).
The prevention and treatment of atherosclerosis aim to reduce the risk factors that cause endothelial dysfunction, modulate the inflammatory response of the arterial wall, stabilize or regress existing plaques, and prevent or treat plaque rupture and its complications. Some of the strategies include:
– Lifestyle modifications: Smoking cessation, regular physical activity, healthy diet, weight management and stress reduction are essential for preventing or slowing down atherosclerosis. These measures can lower blood pressure, blood glucose, LDL cholesterol and inflammation, as well as improve endothelial function and vascular health.
– Pharmacological interventions: Several classes of drugs are available to treat dyslipidemia (statins, ezetimibe, PCSK9 inhibitors), hypertension (ACE inhibitors, ARBs, beta blockers, calcium channel blockers), diabetes (metformin, SGLT2 inhibitors, GLP-1 agonists), inflammation (aspirin, colchicine) and thrombosis (anticoagulants, antiplatelets). These drugs can reduce cardiovascular events by lowering serum levels of harmful substances, improving endothelial function, stabilizing plaques or preventing clot formation.
– Surgical or endovascular procedures: In some cases, when pharmacological therapy is insufficient or contraindicated, or when the plaque causes severe or life-threatening ischemia, surgical or endovascular procedures may be indicated to restore blood flow to the affected organ. These procedures include coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), carotid endarterectomy, carotid stenting, peripheral artery bypass or angioplasty.
Atherosclerosis is a multifactorial and progressive disease that can affect any artery in the body and cause serious complications. Understanding its pathophysiology and risk factors is crucial for developing effective prevention and treatment strategies. Atherosclerosis can be prevented or delayed by adopting a healthy lifestyle and controlling modifiable risk factors. Atherosclerosis can be treated by using pharmacological agents or invasive procedures to reduce plaque burden and improve blood flow.
References:
– Arteriosclerosis / atherosclerosis – Symptoms and causes – Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/arteriosclerosis-atherosclerosis/symptoms-causes/syc-20350569. Accessed October 5, 2023.
– Atherosclerosis | Description, Pathophysiology, Risk Factors, & Treatment | Britannica. https://www.britannica.com/science/atherosclerosis. Accessed October 5, 2023.
– Atherosclerosis: Definition and pathogenesis | Kenhub. https://www.kenhub.com/en/library/anatomy/atherosclerosis. Accessed October 5, 2023.
