Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides

Katey J. Rayner, Christine C. Esau, Farah N. Hussain, Allison L. McDaniel, Stephanie M. Marshall, Janine M. van Gils, Tathagat D. Ray, Frederick J. Sheedy, Leigh Goedeke, Xueqing Liu, Oleg G. Khatsenko, Vivek Kaimal, Cynthia J. Lees, Carlos Fernandez-Hernando, Edward A. Fisher, Ryan E. Temel () and Kathryn J. Moore ()
Additional contact information
Katey J. Rayner: Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine
Christine C. Esau: Regulus Therapeutics
Farah N. Hussain: Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine
Allison L. McDaniel: Wake Forest University School of Medicine
Stephanie M. Marshall: Wake Forest University School of Medicine
Janine M. van Gils: Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine
Tathagat D. Ray: Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine
Frederick J. Sheedy: Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine
Leigh Goedeke: Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine
Xueqing Liu: Regulus Therapeutics
Oleg G. Khatsenko: Regulus Therapeutics
Vivek Kaimal: Regulus Therapeutics
Cynthia J. Lees: Wake Forest University School of Medicine
Carlos Fernandez-Hernando: Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine
Edward A. Fisher: Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine
Ryan E. Temel: Wake Forest University School of Medicine
Kathryn J. Moore: Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine

Nature, 2011, vol. 478, issue 7369, 404-407

Abstract: Manipulating plasma lipids Recent work in mice has shown that microRNA-33a is an important regulator of lipid metabolism and that its inhibition can increase plasma high-density lipoprotein (HDL) and decrease atherosclerosis. Rayner et al. take an important step in translating these findings to non-human primates (African green monkeys), which, like humans and unlike mice, express both miR-33a and miR-33b. They find that anti-miR-33 is effective at inhibiting both miR-33a and miR-33b. As seen in the mouse studies, anti-miR33 raised plasma HDL but had the additional beneficial effect of reducing very low-density lipoprotein triglycerides, making this type of 'antagomir' therapy a candidate method of treating dyslipidaemias that increase cardiovascular disease risk.

Date: 2011
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DOI: 10.1038/nature10486

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