on July 31, 2008
Published online before print July 31, 2008, doi: 10.1161/ATVBAHA.108.171363
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Submitted on November 16, 2007
Accepted on July 23, 2008
Niacin Increases HDL by Reducing Hepatic Expression and Plasma Levels of Cholesteryl Ester Transfer Protein in APOE*3Leiden.CETP Mice
José W.A. van der Hoorn *;
From the Netherlands Organization for Applied Scientific Research-Quality of Life (J.W.A.v.d.H., L.M.H., H.M.G.P.), Gaubius Laboratory, Leiden, The Netherlands; and the Departments of Cardiology (J.W.A.v.d.H., L.M.H., J.W.J.), and General Internal Medicine, Endocrinology, and Metabolic Diseases (W.d.H., J.F.P.B., L.M.H., P.C.N.R.), Leiden University Medical Center, The Netherlands.
* To whom correspondence should be addressed. E-mail: jose.vanderhoorn{at}tno.nl.
Objective—Niacin potently decreases plasma triglycerides and LDL-cholesterol. In addition, niacin is the most potent HDL-cholesterol–increasing drug used in the clinic. In the present study, we aimed at elucidation of the mechanism underlying its HDL-raising effect.
Methods and Results—In APOE*3Leiden transgenic mice expressing the human CETP transgene, niacin dose-dependently decreased plasma triglycerides (up to -77%, P<0.001) and total cholesterol (up to -66%, P<0.001). Concomitantly, niacin dose-dependently increased HDL-cholesterol (up to +87%, P<0.001), plasma apoAI (up to +72%, P<0.001), as well as the HDL particle size. In contrast, in APOE*3Leiden mice, not expressing CETP, niacin also decreased total cholesterol and triglycerides but did not increase HDL-cholesterol. In fact, in APOE*3Leiden.CETP mice, niacin dose-dependently decreased the hepatic expression of CETP (up to -88%; P<0.01) as well as plasma CETP mass (up to -45%, P<0.001) and CETP activity (up to -52%, P<0.001). Additionally, niacin dose-dependently decreased the clearance of apoAI from plasma and reduced the uptake of apoAI by the kidneys (up to -90%, P<0.01).
Conclusion—Niacin markedly increases HDL-cholesterol in APOE*3Leiden.CETP mice by reducing CETP activity, as related to lower hepatic CETP expression and a reduced plasma (V)LDL pool, and increases HDL-apoAI by decreasing the clearance of apoAI from plasma.
Key words: APOE*3Leiden.CETP transgenic mice • CETP • HDL-cholesterol • hyperlipidemia • niacin
Related Article:
- Of Mice and Men: Blowing Away the Cobwebs From the Mechanism of Action of Niacin on HDL Metabolism
- G.F. Watts and D.C. Chan
Arterioscler Thromb Vasc Biol 2008 28: 1892-1895.[Extract] [Full Text] [PDF]
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