Molecular and Cellular Mechanisms of Electronegative Lipoproteins in Cardiovascular Diseases

Abstract

Dysregulation of glucose and lipid metabolism increases plasma levels of lipoproteins and triglycerides, resulting in vascular endothelial damage. Remarkably, the oxidation of lipid and lipoprotein particles generates electronegative lipoproteins that mediate cellular deterioration of atherosclerosis. In this review, we examined the core of atherosclerotic plaque, which is enriched by byproducts of lipid metabolism and lipoproteins, such as oxidized low-density lipoproteins (oxLDL) and electronegative subfraction of LDL (LDL(-)). We also summarized the chemical properties, receptors, and molecular mechanisms of LDL(-). In combination with other well-known markers of inflammation, namely metabolic diseases, we concluded that LDL(-) can be used as a novel prognostic tool for these lipid disorders. In addition, through understanding the underlying pathophysiological molecular routes for endothelial dysfunction and inflammation, we may reassess current therapeutics and might gain a new direction to treat atherosclerotic cardiovascular diseases, mainly targeting LDL(-) clearance.

Keywords: L5 LDL; LDL(−); LOX-1; atherosclerosis; cardiovascular disease; dyslipidemia; electronegative LDL; endothelial dysfunction; lectin-like oxLDL receptor-1; oxLDL; oxidized LDL.

Figure 1

Schematic mechanism of atherosclerosis. LDL: low-density lipoprotein; ROS: reactive oxygen species; oxLDL: oxidized LDL; LOX-1: lectin-like oxidized LDL receptor-1; ADMA: asymmetric dimethylarginine; NO: nitric oxide; NADPH: nicotinamide adenine dinucleotide phosphate; ONOO: peroxynitrite; Bad: BCL2-associated agonist of cell death; Bax: Bcl-2-associated X protein; MCP-1: monocyte chemoattractant protein-1; MCSF: macrophage colony-stimulating factor.

Figure 2

Schematic procedures of lipoprotein metabolism and LDL(−) formation. SREBP: sterol regulatory element-binding protein; PPAR-γ: peroxisome proliferator-activated receptor; CD36: cluster of differentiation 36; TG: triglycerides; apoB100: apolipoprotein B100; VLDL: very low-density lipoprotein; IDL: intermediate-density lipoprotein; LDL: low-density lipoprotein; LDLR: LDL receptor; FFA: free fatty acid.