Interplay between CRP, Atherogenic LDL, and LOX-1 and Its Potential Role in the Pathogenesis of Atherosclerosis

BACKGROUND: Studies have shown that the classic acute-phase protein C-reactive protein (CRP) has pro inflammatory effects on vascular cells and may play a causal role in the pathogenesis of coronary artery disease. A growing body of evidence has suggested that interplay between CRP, lectin-like oxidized LDL receptor-1 (LOX-1), and atherogenic LDL may underlie the mechanism of endothelial dysfunction that leads to atherosclerosis. CONTENT: We review the biochemical evidence for an association of CRP, LOX-1, and either oxidized LDL (OxLDL) or electronegative L5 LDL with the pathogenesis of coronary artery disease. Artificially oxidized OxLDL has been studied extensively for its role in atherogenesis, as has electronegative L5 LDL, which is present at increased levels in patients with increased cardiovascular risks. OxLDL and L5 have been shown to stimulate human aortic endothelial cells to produce CRP, indicating that CRP is synthesized locally in the endothelium. The ligand-binding face (B-face) of CRP has been shown to bind the LOX-1 scavenger receptor and increase LOX-1 expression in endothelial cells, thereby promoting the uptake of OxLDL or L5 by LOX-1 into endothelial cells to induce endothelial dysfunction. SUMMARY: CRP and LOX-11 may form a positive feedback loop with OxLDL or L5 in atherogenesis, whereby increased levels of atherogenic LDL in patients with cardiovascular risks induce endothelial cells to express CRP, which may in turn increase the expression of LOX-1 to promote the uptake of atherogenic LDL into endothelial cells. Further research is needed to confirm a causal role for CRP in atherogenesis. (C) 2015 American Association for Clinical. Chemistry