Pathophysiology of Atherosclerosis

Abstract

Atherosclerosis is the main risk factor for cardiovascular disease (CVD), which is the leading cause of mortality worldwide. Atherosclerosis is initiated by endothelium activation and, followed by a cascade of events (accumulation of lipids, fibrous elements, and calcification), triggers the vessel narrowing and activation of inflammatory pathways. The resultant atheroma plaque, along with these processes, results in cardiovascular complications. This review focuses on the different stages of atherosclerosis development, ranging from endothelial dysfunction to plaque rupture. In addition, the post-transcriptional regulation and modulation of atheroma plaque by microRNAs and lncRNAs, the role of microbiota, and the importance of sex as a crucial risk factor in atherosclerosis are covered here in order to provide a global view of the disease.

Keywords: atheroma plaque; atherosclerosis; endothelial dysfunction; lncRNA; microRNA; microbiota; ocLDL; risk factors.

Figure 1

Effect of flow and WSS patterns at arterial bifurcations on atherosclerotic plaque development. (A) In straight vessel segments, physiological WSS with laminar flow leads to ECs and shows a quiescent characteristic flattened shape when flow disturbance occurs. Lower WSS at the outer vessel wall causes ECs to adopt a cobblestone appearance. (B) Turbulent flow occurs at bifurcations and branch points where the arterial curvature is higher due to flow separation. Disturbed laminar flow or turbulent flow reduces WSS and promotes endothelial dysfunction and LDL infiltration, which constitutes the first step of atheroma plaque formation. On the contrary, low curvature areas of the vascular system subjected to higher shear stress are athero-protected.

Figure 2

Nitric oxygen regulates cardiovascular metabolism and is compromised in the presence of cardiovascular risk factors. eNOS catalyzes the production of NO from L-arginine. NO is an essential metabolite that inhibits the progression of atherosclerosis improving vasorelaxation, angiogenesis, endothelial function, insulin secretion, glucose clearance, and mitochondrial efficiency. On the other hand, it reduces oxidative stress, inflammation, plasma lipid levels, and stenosis. Cardiovascular risk factors, such as hyperlipidemia, hypertension, and diabetes, inhibit eNOS activity upon NF-kβ induction, reducing NO and promoting atherosclerosis development.

Figure 3

Schematic representation of atheroma plaque formation from a healthy artery to plaque rupture underlying the most important events that contribute to its development in each stage.

Figure 4

Different patterns in CVD incidence between women and men.