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Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice.
Arterioscler Thromb Vasc Biol. 2008 Nov; 28(11):2016-22.AT

Abstract

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).

CONCLUSIONS

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.

Authors+Show Affiliations

Netherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands. jose.vanderhoorn@tno.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18669886

Citation

van der Hoorn, José W A., et al. "Niacin Increases HDL By Reducing Hepatic Expression and Plasma Levels of Cholesteryl Ester Transfer Protein in APOE*3Leiden.CETP Mice." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 11, 2008, pp. 2016-22.
van der Hoorn JW, de Haan W, Berbée JF, et al. Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice. Arterioscler Thromb Vasc Biol. 2008;28(11):2016-22.
van der Hoorn, J. W., de Haan, W., Berbée, J. F., Havekes, L. M., Jukema, J. W., Rensen, P. C., & Princen, H. M. (2008). Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 28(11), 2016-22. https://doi.org/10.1161/ATVBAHA.108.171363
van der Hoorn JW, et al. Niacin Increases HDL By Reducing Hepatic Expression and Plasma Levels of Cholesteryl Ester Transfer Protein in APOE*3Leiden.CETP Mice. Arterioscler Thromb Vasc Biol. 2008;28(11):2016-22. PubMed PMID: 18669886.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice. AU - van der Hoorn,José W A, AU - de Haan,Willeke, AU - Berbée,Jimmy F P, AU - Havekes,Louis M, AU - Jukema,J Wouter, AU - Rensen,Patrick C N, AU - Princen,Hans M G, Y1 - 2008/07/31/ PY - 2008/8/2/pubmed PY - 2008/11/7/medline PY - 2008/8/2/entrez SP - 2016 EP - 22 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 28 IS - 11 N2 - 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). CONCLUSIONS: 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. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/18669886/Niacin_increases_HDL_by_reducing_hepatic_expression_and_plasma_levels_of_cholesteryl_ester_transfer_protein_in_APOE_3Leiden_CETP_mice_ L2 - https://www.ahajournals.org/doi/10.1161/ATVBAHA.108.171363?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -