title: Interplay between CRP, Atherogenic LDL, and LOX-1 and Its Potential Role in the Pathogenesis of Atherosclerosis.
abstract: BACKGROUND
  Studies have shown that the classic acute-phase protein C-reactive protein (CRP) has proinflammatory 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.
  
  
  BACKGROUND
  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.
  
  
  CONCLUSIONS
  CRP and LOX-1 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.
authors.affiliation: Department of Vascular and Medicinal Research, Texas Heart Institute, Houston, TX;
authors.forename: Nicole
authors.initials: N
authors.lastname: Stancel
authors.affiliation: Center for Lipid Biosciences, Kaohsiung Medical University (KMU) Hospital, KMU, Kaohsiung, Taiwan; Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan;
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Center for Lipid Biosciences, Kaohsiung Medical University (KMU) Hospital, KMU, Kaohsiung, Taiwan; Lipid Science and Aging Research Center, KMU, Kaohsiung, Taiwan; Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, KMU, Kaohsiung, Taiwan;
authors.forename: Liang-Yin
authors.initials: LY
authors.lastname: Ke
authors.affiliation: Center for Lipid Biosciences, Kaohsiung Medical University (KMU) Hospital, KMU, Kaohsiung, Taiwan; Department of Internal Medicine, KMU Hospital, Kaohsiung, Taiwan; Faculty of Medicine, College of Medicine, KMU, Kaohsiung, Taiwan;
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Chu
authors.affiliation: Department of Vascular and Medicinal Research, Texas Heart Institute, Houston, TX;
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Physiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; cchen@texasheart.org t-sawamura@umin.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
authors.affiliation: Department of Vascular and Medicinal Research, Texas Heart Institute, Houston, TX; Center for Lipid Biosciences, Kaohsiung Medical University (KMU) Hospital, KMU, Kaohsiung, Taiwan; Lipid Science and Aging Research Center, KMU, Kaohsiung, Taiwan; Cardiovascular Research Center, China Medical University (CMU) Hospital, CMU, Taichung, Taiwan; Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX; Current affiliation: New York Heart Research Foundation, Mineola, NY. cchen@texasheart.org t-sawamura@umin.ac.jp.
authors.forename: Chu-Huang
authors.initials: CH
authors.lastname: Chen
mesh_terms: D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism*; D002097:C-Reactive Protein / Q000737:chemistry / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000378:metabolism; D042783:Endothelial Cells; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000097:blood / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; C574964:low-density lipoprotein L5, human; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein