IMR Press / RCM / Volume 23 / Issue 6 / DOI: 10.31083/j.rcm2306212
Open Access Review
Mechanism of Hypercholesterolemia-Induced Atherosclerosis
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1 Department of Physiology (APP), College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada
2 Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada
*Correspondence: (Kailash Prasad)
Academic Editors: Karol E. Watson and Morris Karmazyn
Rev. Cardiovasc. Med. 2022, 23(6), 212;
Submitted: 12 February 2022 | Revised: 6 May 2022 | Accepted: 7 May 2022 | Published: 9 June 2022
(This article belongs to the Special Issue Highlighting Excellence in Cardiovascular Research in Canada)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Hypercholesterolemia is involved in the development of atherosclerosis and is a risk factor for coronary artery disease, stroke, and peripheral vascular disease. This paper deals with the mechanism of development of hypercholesterolemic atherosclerosis. Hypercholesterolemia increases the formation of numerous atherogenic biomolecules including reactive oxygen species (ROS), proinflammatory cytokines [interleukin (IL)-1, IL-2, IL-6, IL-8, tumor necrosis factor-alpha (TNF-α)], expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte chemoattractant protein-1 (MCP-1), granulocyte macrophage-colony stimulating factor (GM-CSF) and numerous growth factors [insulin-like growth factor-1 (IGF-1), platelet-derived growth factor-1 (PDGF-1) and transforming growth factor-beta (TGF-β)]. ROS mildly oxidizes low-density lipoprotein-cholesterol (LDL-C) to form minimally modified LDL (MM-LDL) which is further oxidized to form oxidized LDL (OX-LDL). Hypercholesterolemia also activates nuclear factor-kappa-B (NF-κB). The above atherogenic biomolecules are involved in the development of atherosclerosis which has been described in detail. Hypercholesterolemia also assists in the development of atherosclerosis through AGE (advanced glycation end-products)-RAGE (receptor for AGE) axis and C-reactive protein (CRP). Hypercholesterolemia is associated with increases in AGE, oxidative stress [AGE/sRAGE (soluble receptor for AGE)] and C-reactive protein, and decreases in the sRAGE, which are known to be implicated in the development of atherosclerosis. In conclusion, hypercholesterolemia induces atherosclerosis through increases in atherogenic biomolecules, AGE-RAGE axis and CRP.

reactive oxygen species
cell adhesion molecules
advanced glycation end products
C-reactive protein
nuclear factor-kappa B
atherogenic biomolecules
Fig. 1.
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