title: Revising the high-density lipoprotein targeting strategies - insights from human and preclinical studies.
abstract: In recent years, the high-density lipoprotein (HDL) hypothesis has been challenged. Several completed randomized clinical trials continue to fall short in demonstrating HDL, or at least HDL-cholesterol (HDL-C) levels, as being a consistent target in the prevention of cardiovascular diseases. However, population studies and findings in lipid modifying trials continue to strongly support HDL-C as a superb risk predictor. It is increasingly evident that the complexity of HDL metabolism confounds the use of HDL-C concentration as a unified target. However, important insights continue to emerge from the post hoc analyses of recently completed (i) fibrate-based FIELD and ACCORD trials, including the unexpected beneficial effect of fibrates in microvascular diseases, (ii) the niacin-based AIM-HIGH and HPS2-THRIVE studies, (iii) recombinant HDL-based as well as (iv) the completed CETP inhibitor-based trials. These together with on-going mechanistic studies on novel pathways, which include the unique roles of microRNAs, post-translational remodeling of HDL and novel pathways related to HDL modulators will provide valuable insights to guide how best to refocus and redesign the conceptual framework for selecting HDL-based targets.
authors.affiliation: Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital , Toronto, Ontario , Canada .
authors.forename: Dinushan
authors.initials: D
authors.lastname: Nesan
authors.forename: Dominic S
authors.initials: DS
authors.lastname: Ng
mesh_terms: D002318:Cardiovascular Diseases; D008076:Cholesterol, HDL; D058607:Fibric Acids; D006801:Humans; D006949:Hyperlipidemias; D000960:Hypolipidemic Agents; D035683:MicroRNAs; D009525:Niacin
chemical_list: D008076:Cholesterol, HDL; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D035683:MicroRNAs; D009525:Niacin
keywords: ABCA1; CETP; LCAT; apoA1; fibrates; high-density lipoprotein cholesterol; microRNA; niacin; recombinant HDL; reverse cholesterol transport