title: HDL cholesterol in cardiovascular diseases: the good, the bad, and the ugly?
abstract: Atherosclerotic cardiovascular diseases are the leading cause of death in developed and developing countries. HDL-raising therapeutic modalities (such as cholesterol ester transferase protein (CETP) inhibitors) are being developed to combat these diseases. However, recent setback of two CETP inhibitors (Torcetrapib and Dalcetrapib) has highlighted the importance of measuring qualitative functionality of HDL particles, rather than focusing quantitatively on HDL cholesterol serum concentrations. It has been known that, HDL from patients with coronary artery disease (CAD) (i.e., HDL(CAD)) limits the anti-inflammatory and endothelial repair properties of normal HDL, due to the activation of lectin-like oxidized LDL receptor-1 (LOX-1), thereby causing failure in endothelial nitric oxide (NO) production. A more recent study (Immunity 2013; 38: 754-768) also demonstrates that HDL from patients with chronic kidney dysfunction (CKD) (i.e., HDL(CKD)), unlike its healthy counterpart (i.e., HDL(Healthy)), promotes superoxide production, reduces NO bioavailability and raises blood pressure via toll-like receptor-2 (TLR-2) activation. This study provides novel insights into understanding why HDL-raising agents failed to demonstrate beneficial effects on cardiovascular mortality in large clinical trials and why CKD accelerates the development of atherosclerosis in CAD patients. Further research is warranted to elucidate whether HDL(CKD) and HDL(CAD) participate in other cellular processes in atherosclerosis, such as foam cell formation, the proliferation and migration of smooth muscle cells, and most importantly, plaque destabilization.
authors: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China. Electronic address: suo-wen.xu@nih.gov.
authors: Suowen
authors: S
authors: Xu
authors: Zhiping
authors: Z
authors: Liu
authors: Peiqing
authors: P
authors: Liu
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology*; D006801:Humans; D006973:Hypertension / Q000276:immunology*; D007674:Kidney Diseases / Q000276:immunology*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
chemical_list: D008075:Lipoproteins, HDL; D051195:Toll-Like Receptor 2
keywords: Atherosclerosis; Chronic kidney disease; Coronary artery disease; HDL; LOX-1; TLR-2