Apolipoproteins as potential communicators play an essential role in the pathogenesis and treatment of early atherosclerosis

Abstract

Atherosclerosis as the leading cause of the cardiovascular disease is closely related to cholesterol deposition within subendothelial areas of the arteries. Significantly, early atherosclerosis intervention is the critical phase for its reversal. As atherosclerosis progresses, early foam cells formation may evolve into fibrous plaques and atheromatous plaque, ulteriorly rupture of atheromatous plaque increases risks of myocardial infarction and ischemic stroke, resulting in high morbidity and mortality worldwide. Notably, amphiphilic apolipoproteins (Apos) can concomitantly combine with lipids to form soluble lipoproteins that have been demonstrated to associate with atherosclerosis. Apos act as crucial communicators of lipoproteins, which not only can mediate lipids metabolism, but also can involve in pro-atherogenic and anti-atherogenic processes of atherosclerosis via affecting subendothelial retention and aggregation of low-density lipoprotein (LDL), oxidative modification of LDL, foam cells formation and reverse cholesterol transport (RCT) in macrophage cells. Correspondingly, Apos can be used as endogenous and/or exogenous targeting agents to effectively attenuate the development of atherosclerosis. The article reviews the classification, structure, and relationship between Apos and lipids, how Apos serve as communicators of lipoproteins to participate in the pathogenesis progression of early atherosclerosis, as well as how Apos as the meaningful targeting mass is used in early atherosclerosis treatment.

Triglyceride-rich lipoproteins and cardiovascular diseases

“…ApoB emerges as a pivotal player in the proatherogenic cascade. By interacting with proteoglycans in the extracellular matrix, ApoB facilitates the retention and aggregation of surplus cholesterol-rich lipoproteins within the subendothelium of the arterial wall-an essential initial step in AS formation (41,42). Lipoproteins containing ApoB with a diameter less than 70 nm, including CM remnants, VLDL, VLDL remnants, IDL, and LDL, can efficiently traverse the intact endothelium, allowing products from TRLs metabolism, except de novo CM, to accumulate beneath the vascular endothelium (43).…”

High Apolipoprotein B/Apolipoprotein A1 is Associated with Vitamin D Deficiency Among Type 2 Diabetes Patients

“…Accumulating evidence has demonstrated that although apolipoproteins have often been ignored in the biochemical detection of blood lipids, their contribution to the pathogenesis of early atherosclerosis may exceed our imagination. [25][26][27][28] As a communicator of lipoprotein, apolipoprotein can mediate the activation of vascular endothelial cells (ECs), and the activated vascular ECs produce interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and other cytokines. These factors stimulate the recruitment of monocytes and adhesion to ECs, prompting monocytes to pass through endothelial tissues and transform into macrophages.…”

“…These factors stimulate the recruitment of monocytes and adhesion to ECs, prompting monocytes to pass through endothelial tissues and transform into macrophages. 25 Apo B in apolipoprotein acts as a ligand-mediated LDL to bind to the LDL receptor (LDLR) to promote cholesterol uptake in peripheral tissues. Meanwhile, apo B causes excessive LDL to accumulate under the vascular endothelial by interacting with proteoglycan in the extracellular matrix, initiating the formation of atherosclerosis.…”