INFLAMMATION IN ATHEROSCLEROSIS: PATHOPHYSIOLOGY AND MECHANISMS

Abstract

Atherosclerosis is a major cause of cardiovascular diseases (CVDs) in the world hence the high disease burden and mortality. It is not considered as a passive process of lipid deposits but is now being addressed as a chronic inflammatory disease, where lipids, immune cells, and vascular constituents interact in a complex manner. Pathogenesis begins with the endothelial damage predetermined by hyperlipidemia, hypertension, and oxidative stress leading to the recruitment of monocytes upon the eating of oxidized LDL in the shape of foam cells. The inflammatory environment depends on foam cells and T-lymphocytes that promote the growth and development of plaque. Lipid-containing necrotic cores develop histologically with time and cause deposition of fibrous tissue and disruption of the plaque, which culminates into thrombus formation and acute cardiovascular outcome, including myocardial infarction and stroke. The inflammatory cytokines such as interleukin-1 beta (IL-1B), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-A) are important in endothelial activation, leukocyte recruitment, and destabilization of the plaque. Higher biomarkers such as high-sensitivity C-reactive protein (hs-CRP) are used as predictor markers of cardiovascular risk. The identification of inflammation as the leading cause of atherosclerosis has led to the emergence of specific anti-inflammatory agents, such as IL-1 and IL-6 inhibitors, which have investigated in the prevention of cardiovascular events.