title: Pharmacologic augmentation of high-density lipoproteins: mechanisms of currently available and emerging therapies.
abstract: OBJECTIVE
  With the limited effects of low-density lipoprotein-based lipid intervention, more attention is being paid to drugs that augment or mimic high-density lipoprotein's beneficial effects. A thorough understanding of the anti-atherogenic effects of high-density lipoprotein, and the mechanisms of existing or emerging high-density lipoprotein-based therapies, is essential for rational strategy for the prevention of cardiovascular disease.
  
  
  RESULTS
  High-density lipoprotein mediates its beneficial effects through reverse cholesterol transport and direct anti-inflammatory effects of apolipoprotein AI and other component parts. Currently available drugs increase high-density lipoprotein-C through increasing apoAI synthesis (statins, fibrates) and decreasing apolipoprotein AI catabolism (niacin). Cholesteryl ester transfer protein inhibitors dramatically raise high-density lipoprotein-C, but clinical data are still required to verify their cardioprotective effects. Novel therapies such as apolipoprotein AImilano, apolipoprotein AI mimetic peptide, and exogenous phospholipids show tremendous promise as treatments for atherosclerosis.
  
  
  CONCLUSIONS
  High-density lipoprotein and its defining functional protein apoAI prevent atherosclerosis through reverse cholesterol transport and other direct effects. Research has led to the development of novel therapies that increase high-density lipoprotein-C or that mimic direct anti-atherogenic effects of apolipoprotein AI. As these emerging therapies find a place in clinical medicine, we can anticipate preventing a much higher degree of cardiovascular events.
authors.affiliation: Atherosclerosis Research Center, VA Long Beach Healthcare System, 5901 East 7th Street (11-1111), Long Beach, CA 90822, USA.
authors.forename: C Daniel
authors.initials: CD
authors.lastname: Meyers
authors.forename: Moti L
authors.initials: ML
authors.lastname: Kashyap
mesh_terms: D000577:Amides; D000818:Animals; D016632:Apolipoprotein A-I / Q000627:therapeutic use; D050197:Atherosclerosis / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D002995:Clofibric Acid / Q000627:therapeutic use; D004952:Esters; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008075:Lipoproteins, HDL / Q000627:therapeutic use*; D013438:Sulfhydryl Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use
chemical_list: D000577:Amides; D016632:Apolipoprotein A-I; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D004952:Esters; D006023:Glycoproteins; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D013438:Sulfhydryl Compounds; D045162:Thiazolidinediones; C411602:dalcetrapib; D002995:Clofibric Acid