From the Guidelines
Atherosclerosis develops through an inflammatory process triggered by damage to the inner lining of arteries, leading to the accumulation of fatty deposits and immune cells, ultimately resulting in plaque formation and potential rupture. This process is supported by evidence from the Centers for Disease Control and Prevention and the American Heart Association, which highlights the role of inflammation in atherosclerosis 1. The development of atherosclerosis involves several key steps, including:
- Damage to the endothelium by factors such as high blood pressure, smoking, high cholesterol, or diabetes
- Infiltration of LDL cholesterol into the artery wall, triggering an inflammatory response
- Activation of immune cells, including macrophages, which attempt to digest the LDL particles
- Transformation of macrophages into foam cells, which die and contribute to the growing core of fatty material
- Migration and proliferation of smooth muscle cells, which produce collagen and form a fibrous cap over the lipid core
- Growth and potential rupture of the plaque, leading to blood clot formation and potential blockage of blood flow. According to 1, the inflammatory cascade involved in atherosclerosis may have sources other than an atherosclerotic coronary artery, including systemic inflammation and local infections.
From the Research
Atherosclerosis Development
Atherosclerosis is a complex disease that develops through a series of events, including:
- Endothelium activation, followed by a cascade of events such as accumulation of lipids, fibrous elements, and calcification, triggering vessel narrowing and activation of inflammatory pathways 2
- Accumulation of low-density lipoprotein cholesterol within the arterial wall of medium and large arteries, stimulating the infiltration of immune cells, such as monocytes/macrophages and T-lymphocytes 3
- Formation of lipid-laden foam cells, which can lead to increased accumulation of dead cells, cellular debris, and extracellular cholesterol, forming a lipid-rich necrotic core 3
- Migration and proliferation of vascular smooth muscle cells from the arterial media into the intima layer, taking up available lipids to become foam cells and producing extracellular matrix proteins such as collagen and elastin 3
Key Factors Contributing to Atherosclerosis
Several factors contribute to the development of atherosclerosis, including:
- Oxidative stress, inflammation, hypertension, and hyperlipidemia, which influence atherogenesis 3
- Genetic and environmental factors, such as family history, which is the most significant independent risk factor for coronary artery disease (CAD) 4
- Genetic polymorphisms, which significantly influence susceptibility to atherosclerotic vascular diseases 5
- Lipid accumulation and inflammation, which are closely linked and interact with each other in the pathogenesis of atherosclerosis 6
Cellular and Molecular Mechanisms
The cellular and molecular mechanisms involved in atherosclerosis development include:
- Dysfunction of lipid homeostasis and signaling pathways that control inflammation 6
- Role of microRNAs and long non-coding RNAs (lncRNAs) in regulating HDL biogenesis, cholesterol efflux, lipid metabolism, smooth muscle proliferation, and controlling inflammation 6
- Importance of sex as a crucial risk factor in atherosclerosis, with post-transcriptional regulation and modulation of atheroma plaque by microRNAs and lncRNAs 2