Immune system and atherosclerosis: Hostile or friendly relationship

Abstract

Coronary artery disease has remained a major health challenge despite enormous progress in prevention, diagnosis, and treatment strategies. Formation of atherosclerotic plaque is a chronic process that is developmentally influenced by intrinsic and extrinsic determinants. Inflammation triggers atherosclerosis, and the fundamental element of inflammation is the immune system. The immune system involves in the atherosclerosis process by a variety of immune cells and a cocktail of mediators. It is believed that almost all main components of this system possess a profound contribution to the atherosclerosis. However, they play contradictory roles, either protective or progressive, in different stages of atherosclerosis progression. It is evident that monocytes are the first immune cells appeared in the atherosclerotic lesion. With the plaque growth, other types of the immune cells such as mast cells, and T lymphocytes are gradually involved. Each cell releases several cytokines which cause the recruitment of other immune cells to the lesion site. This is followed by affecting the expression of other cytokines as well as altering certain signaling pathways. All in all, a mix of intertwined interactions determine the final outcome in terms of mild or severe manifestations, either clinical or subclinical. Therefore, it is of utmost importance to precisely understand the kind and degree of contribution which is made by each immune component in order to stop the growing burden of cardiovascular morbidity and mortality. In this review, we present a comprehensive appraisal on the role of immune cells in the atherosclerosis initiation and development.

Inflammation: the next target for secondary prevention in coronary artery disease

“…9 Endothelial injury, such as hypertension and oxidative stress, allows monocytes to enter the artery wall. 9 LDL becomes entrapped in the intimal layer of the coronary artery, where monocytes transform into macrophages and engulf the LDL to form foamy macrophages. 10 Macrophages also stimulate an adaptive immune response by activating T cells.…”

“…9 T cells such as Th1 cells release pro-inflammatory cytokines (eg, IL-1β, TNFα and interferon [IFN]γ). 9 Other immune cells such as neutrophils and mast cells also release pro-inflammatory cytokines (eg, IFNγ, TNFα and IL-6), which further recruit immune cells and inflammation. 9 This all contributes to the chronic inflammatory process of atherosclerosis (Box 1).…”

“…9 Other immune cells such as neutrophils and mast cells also release pro-inflammatory cytokines (eg, IFNγ, TNFα and IL-6), which further recruit immune cells and inflammation. 9 This all contributes to the chronic inflammatory process of atherosclerosis (Box 1). The high turnover of inflammatory cells leads to cell death and development of a necrotic core within the atherosclerotic plaque.…”

“…Poor lipid metabolism results in stimulation of the immune system, with some epitopes of oxidised low‐density lipoprotein (LDL) triggering an innate and adaptive immune response 9 . Endothelial injury, such as hypertension and oxidative stress, allows monocytes to enter the artery wall 9 .…”

Genetic and Epigenetic Regulation of Lipoxygenase Pathways and Reverse Cholesterol Transport in Atherogenesis

“…Accumulating evidence suggests that the development and progression of atherosclerosis are associated with impaired mechanisms of the innate immune system [ 10 , 11 ]. Indeed, macrophages, which perform many functions of the innate immune system, are actively involved in the pathogenesis of atherosclerosis [ 12 ].…”