title: HDL-Targeting Therapeutics: Past, Present and Future.
abstract: Large-scale epidemiological studies firmly established the association between low plasma levels of high-density lipoprotein-cholesterol (HDL-C) and elevated risk of cardiovascular disease. This relationship is thought to reflect the key biological function of HDL, which involves reverse cholesterol transport from the arterial wall to the liver for further excretion from the body. Other aspects of the cardioprotective HDL functionality include antioxidative, anti-inflammatory, anti-apoptotic, anti-thrombotic, vasodilatory, anti-infectious and antidiabetic activities. Over the last decades, wide interest in HDL as an athero- and cardioprotective particle has resulted in the development of HDL-C raising as a therapeutic approach to reduce cardiovascular risk. Several strategies to increase circulating HDL-C concentrations were developed that primarily included use of niacin and fibrates as potent HDL-C raising agents. In the statin era, inhibition of cholesteryl ester transfer protein, infusion of artificially reconstituted HDL and administration of apolipoprotein A-I mimetics were established as novel approaches to raise HDL-C. More recently, other strategies targeting HDL metabolism, such as upregulation of apolipoprotein A-I production by the liver, were added to the list of HDL therapeutics. This review summarises current knowledge of novel HDL-targeting therapies and discusses perspectives of their use.
authors: Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow. Russian Federation.
authors: Emile
authors: E
authors: Zakiev
authors: INSERM UMR_S 1166, Faculte de Medecine Pitie-Salpetriere, Bld de L&#39;Hopital 91, 75013 Paris, France; University of Pierre and Marie Curie - Paris 6, Paris. France.
authors: Ma
authors: M
authors: Feng
authors: INSERM UMR_S 1166, Faculte de Medecine Pitie-Salpetriere, Bld de L&#39;Hopital 91, 75013 Paris, France; University of Pierre and Marie Curie - Paris 6, Paris. France.
authors: Vasily
authors: V
authors: Sukhorukov
authors: INSERM UMR_S 1166, Faculte de Medecine Pitie-Salpetriere, Bld de L&#39;Hopital 91, 75013 Paris. France.
authors: Anatol
authors: A
authors: Kontush
mesh_terms: D016632:Apolipoprotein A-I / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000378:metabolism / Q000517:prevention & control; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D058607:Fibric Acids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D009525:Niacin / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D009525:Niacin
keywords: Atherosclerosis; CETP; HDL; apoA-I; cardiovascular disease; lipoprotein; miRNA; rHDL