Review Pathophysiology of Atherosclerosis

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Review Pathophysiology of Atherosclerosis

Abstract: Atherosclerosis is the main risk factor for cardiovascular disease, 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.

One. Introduction

Atherosclerosis is a disease that is characterized by the accumulation of lipids, fibrous elements, and calcification within the large arteries. This process is initiated by endothelium activation, followed by a cascade of events, which implies the vessel narrowing and activation of inflammatory pathways leading to atheroma plaque formation. Altogether, these processes result in cardiovascular complications that remain as the leading cause of death worldwide.

In this study, we aimed to review the mechanism of development of atherosclerosis, including endothelial dysfunction, fatty streak formation, fibrous plaque formation, and plaque rupture. This review approaches the pathophysiology of atherosclerosis from a broad perspective, examining the pathological and biochemical processes of atherosclerotic plaque formation and growth. In addition, this review summarizes the current understanding of the involvement of microRNAs and lncRNAs in post-transcriptional regulation and modulation of atheroma plaque and atherogenesis. Non-traditional drivers of atherosclerosis-such as disturbed sleep, physical inactivity, the microbiome, 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.

Two. Endothelium

Three. Atherosclerosis Initiation and Fatty Streak Formation

Three point one. Endothelial Dysfunction in Atherosclerosis Development

Three point one point one. Hemodynamic Forces and Endothelial Dysfunction

Three point one point two. The Role of Nitric Oxide in Endothelial Dysfunction

Three point two. LDL Infiltration

LDL Modifications in the Intima

Three point three. Endothelial Activation

Three point four. Monocyte Recruitment and Foam Cell Formation

Three point five. Contribution of VSMCs to Foam Cell Population

Four. Fibrous Plaque Development

Four point one. Fibrous Cap

Four point two. Necrotic Core

Four point three. Plaque Calcification

Five. Plaque Stability and Rupture

Five point two. Plaque Rupture and Thrombus Formation

Five point three. Clinical Complications

Six. Inflammation in Atherosclerosis

Seven. Post-Transcriptional Regulation of Atherosclerotic Plaques

Seven point one. microRNAs

Seven point one point one. microRNAs in Atherosclerotic Plaque Initiation and Progression

Seven point one point two. miRNAs and Atherosclerotic Plaque Rupture

Seven point one point three. Distinct miRNA Regulation of VSMC and EC Function

Seven point two. lncRNAs

Nine. Sex as an Important Risk Factor in Atherosclerosis

Nine point one. Impact of Plaque Size and Morphology between Sexes

Nine point two. Clinical Implications

Ten. Cigarette-Smoking-Induced Atherosclerosis

Molecular Mechanisms Underlying Clinical Smoking-Induced Atherosclerosis

Eleven. Conclusions

Overview

This review outlines the key mechanisms of atherosclerosis, focusing on endothelial dysfunction, lipid accumulation, and the roles of genetic and environmental factors, including microRNAs and the microbiome. It provides a comprehensive overview of both traditional and non-traditional risk factors influencing disease progression.

Key Points

1Atherosclerosis is the leading cause of cardiovascular disease and mortality worldwide
2Endothelial dysfunction is the initial trigger for atherosclerosis development
3Hemodynamic forces significantly influence vascular health and plaque formation
4Interactions between microRNAs and lncRNAs play a role in atheroma regulation
5Understanding both genetic and lifestyle factors is crucial for addressing atherosclerosis risk

Details

Authors: Shifa Jebari-Benslaiman, Unai Galicia-García, Asier Larrea-Sebal, Javier Rekondo Olaetxea, Iraide Alloza, Koen Vandenbroeck, Asier Benito-Vicente, César Martín
Category: Health and Medicine

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