From the Guidelines
The alteration in body function that creates fatty streaks in arterial walls, specifically atherosclerosis, is the accumulation of lipid in the intima of arteries due to elevated levels of triglyceride-rich lipoproteins and remnant cholesterol 1.
Key Factors
- Triglyceride-rich lipoproteins can be taken up directly by macrophages, turning them into foam cells rich in indigestible cholesterol droplets, which is a hallmark of atherosclerotic plaques 1.
- Remnant cholesterol is causally associated with low-grade inflammation, which contributes to the development of atherosclerosis 1.
- LDL cholesterol is not directly associated with low-grade inflammation, but modified LDL particles can be taken up by macrophages, leading to foam cell formation and atherosclerosis 1, 2.
Pathophysiological Process
The process of atherosclerosis begins with the accumulation of lipid in the intima of arteries, forming fatty streaks, which can progress to arterial plaque through endothelial activation and dysfunction, smooth muscle cell migration and proliferation, collagen production, and arterial remodeling 3.
Risk Factors
Disorders of lipid metabolism, such as elevated triglycerides and remnant cholesterol, are major atherogenic risk factors, and inflammation plays a crucial role in the genesis of acute coronary syndromes 3.
Clinical Implications
Understanding the pathophysiological significance of the biological composition of the arterial plaque and its fibrous cap is essential for the prevention and management of cardiovascular disease 3.
From the Research
Alteration in Body Function
The alteration in body function that creates fatty streaks in arterial walls, specifically atherosclerosis, is a complex process involving multiple cellular and molecular mechanisms.
- The formation of fatty streaks is initiated by the adhesion of monocytes to a dysfunctional endothelium, which is caused by factors such as hyperlipidaemia, hypertension, or diabetes 4.
- The monocytes then migrate into the vessel wall and become macrophages, which ingest lipid particles and become foam cells, leading to the formation of fatty streaks 4, 5.
- The progression of fatty streaks to fibrous plaques involves the activation of smooth muscle cells, the production of matrix-degrading enzymes, and the release of cytokines, which mediate an immune response 4.
- The role of lipids, particularly low-density lipoprotein (LDL) cholesterol, oxidized LDL (oxLDL) cholesterol, and small dense LDL (sdLDL), in the onset and progression of atherosclerosis has been extensively studied 6, 7.
- The oxidation of lipids in LDLs trapped in the extracellular matrix of the subendothelial space activates an inflammatory response, leading to the development of fatty streaks and the progression of atherosclerosis 6.
Key Cellular and Molecular Mechanisms
- The major cells involved in the development of atherosclerosis are monocytes/macrophages, endothelial cells, smooth muscle cells, and T lymphocytes 4, 5.
- The interaction between these cells and the release of growth factors and cytokines play a crucial role in the formation and progression of atherosclerotic lesions 4, 5.
- Hemodynamic factors, such as low shear stress, can contribute to atherogenesis by prolonging the residence time of atherogenic particles on the endothelium 8.
- Genetic factors can also influence an individual's susceptibility to atherosclerosis by affecting lipid metabolism and the inflammatory response 6.