Niacin Increases HDL by Reducing Hepatic Expression and Plasma Levels of Cholesteryl Ester Transfer Protein in APOE*3Leiden.CETP Mice

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. (Arterioscler Thromb Vase Biol. 2008;28:2016-2022)