Apo A-I Modulating Therapies
- 90 Downloads
The substantial residual risk of cardiovascular events despite the implementation of effective lowering of low-density lipoprotein cholesterol highlights the need to develop additional cardioprotective therapies. Evidence from population and animal studies suggests that high-density lipoproteins (HDLs), the protective lipid particles, may represent a target for therapeutic modification. As a result intensive efforts are in progress to develop new agents that promote HDL activity. Among these different approaches, a range of strategies that target apolipoprotein A-I, the major protein carried on HDL, are being evaluated.
KeywordsApolipoprotein A-I High-density lipoproteins Risk factors Atherosclerosis Lipids Coronary artery disease
Conflicts of interest: S.J. Nicholls: has been a consultant for Roche, Merck, Sanofi-Aventis, Omthera, AstraZeneca, and Pfizer; and has received grant support from AstraZeneca, Eli Lilly, Resverlogix, Anthera, Roche, and Novartis.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.•• Vaisar T, Pennathur S, Green PS, et al. Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL. J Clin Invest. 2007;117:746–56. This paper characterizes a substantial number of proteins carried on HDL particles. PubMedCrossRefGoogle Scholar
- 19.Cui Y, Watson DJ, Girman CJ, et al. Effects of increasing high-density lipoprotein cholesterol and decreasing low-density lipoprotein cholesterol on the incidence of first acute coronary events (from the Air Force/Texas Coronary Atherosclerosis Prevention Study). Am J Cardiol. 2009;104:829–34.PubMedCrossRefGoogle Scholar
- 20.Athyros VG, Mikhailidis DP, Papageorgiou AA, et al. Effect of atorvastatin on high density lipoprotein cholesterol and its relationship with coronary events: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study. Curr Med Res Opin. 2004;20:627–37.PubMedCrossRefGoogle Scholar
- 21.Jun M, Foote C, Lv J, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 375:1875–84.Google Scholar
- 32.Nicholls SJ, Tuzcu EM, Brennan DM, Tardif JC, Nissen SE. Cholesteryl ester transfer protein inhibition, high-density lipoprotein raising, and progression of coronary atherosclerosis: insights from ILLUSTRATE (Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation). Circulation. 2008;118:2506–14.PubMedCrossRefGoogle Scholar
- 42.• Waksman R, Torguson R, Kent KM, et al. A first-in-man, randomized, placebo-controlled study to evaluate the safety and feasibility of autologous delipidated high-density lipoprotein plasma infusions in patients with acute coronary syndrome. J Am Coll Cardiol. 2010;55:2727–35. This paper shows evidence that delipidated HDL promotes regression of coronary atherosclerosis.PubMedCrossRefGoogle Scholar
- 43.Bailey D, Jahagirdar R, Gordon A, et al. RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo. J Am Coll Cardiol. 55:2580–9.Google Scholar
- 45.Sherman CB, Peterson SJ, Frishman WH. Apolipoprotein A-I mimetic peptides: a potential new therapy for the prevention of atherosclerosis. Cardiol Rev. 18:141–7.Google Scholar
- 49.Wang Z, Nicholls SJ, Rodriguez ER, et al. Protein carbamylation links inflammation, smoking, uremia and atherogenesis. Nat Med. 2007.Google Scholar