The immunology of atherosclerosis

Abstract

Cardiovascular disease is the leading cause of death worldwide, both in the general population and among patients with chronic kidney disease (CKD). In most cases, the underlying cause of the cardiovascular event is atherosclerosis - a chronic inflammatory disease. CKD accelerates atherosclerosis via augmentation of inflammation, perturbation of lipid metabolism, and other mechanisms. In the artery wall, subendothelial retention of plasma lipoproteins triggers monocyte-derived macrophages and T helper type 1 (T1) cells to form atherosclerotic plaques. Inflammation is initiated by innate immune reactions to modified lipoproteins and is perpetuated by T1 cells that react to autoantigens from the apolipoprotein B100 protein of LDL. Other T cells are also active in atherosclerotic lesions; regulatory T cells inhibit pathological inflammation, whereas T17 cells can promote plaque fibrosis. The slow build-up of atherosclerotic plaques is asymptomatic, but plaque rupture or endothelial erosion can induce thrombus formation, leading to myocardial infarction or ischaemic stroke. Targeting risk factors for atherosclerosis has reduced mortality, but a need exists for novel therapies to stabilize plaques and to treat arterial inflammation. Patients with CKD would likely benefit from such preventive measures.

The Role of CXCR3 and Associated Chemokines in the Development of Atherosclerosis and During Myocardial Infarction

“…It seems that the activation of the plaque rather than the degree of coronary stenosis precipitates ischemia and infarction. Endothelial erosion or plaque rupture was found to be responsible for the majority of coronary thrombotic events (1, 9) (Box 1). …”

“…The Th1 cells recruited to the lesion recognize LDL as antigen and produce proinflammatory mediators such as interferon-gamma (IFN-γ) and tumor necrosis factor (TNF) (3, 8, 9). IFN-γ is the major proatherogenic cytokine, promoting local expression of adhesion molecules, cytokines and chemokines such as CXCL9, CXCL10, and CXCL11 and their main receptor CXCR3 by macrophages and endothelial cells (10).…”

Atherosclerosis: Beyond the lipid storage hypothesis. The role of autoimmunity

“…7 A fraction of plasma circulating LDL reaches the vascular subendothelial space and subsequently is entrapped in proteoglycans of extracellular matrix, 8 especially in atheromatic prone sites of the vascular system as defined by the local hemodynamic properties. 7 A fraction of plasma circulating LDL reaches the vascular subendothelial space and subsequently is entrapped in proteoglycans of extracellular matrix, 8 especially in atheromatic prone sites of the vascular system as defined by the local hemodynamic properties.…”

Cellular Structure of Atherosclerostic Plagues

“…Данный процесс лежит в основе формирования начального очага поражения стенок сосудов. Макроскопически этот процесс определяется как липидная полоска на интиме [31][32][33]. Таким образом, существенное влияние на процессы формирования, стабилизации АСБ или на развитие осложненного атеросклеротического поражения оказывает баланс между функциональной активностью М1 и М2 субпопуляций макрофагов.…”