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-)], 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-)].
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-B). 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.