Niacin Reduces Atherosclerosis Development in APOE*3Leiden.CETP Mice Mainly by Reducing NonHDL-Cholesterol
Open Access
- 19 June 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (6), e66467
- https://doi.org/10.1371/journal.pone.0066467
Abstract
Niacin potently lowers triglycerides, mildly decreases LDL-cholesterol, and largely increases HDL-cholesterol. Despite evidence for an atheroprotective effect of niacin from previous small clinical studies, the large outcome trials, AIM-HIGH and HPS2-THRIVE did not reveal additional beneficial effects of niacin (alone or in combination with laropiprant) on top of statin treatment. We aimed to address this apparent discrepancy by investigating the effects of niacin without and with simvastatin on atherosclerosis development and determine the underlying mechanisms, in APOE*3Leiden.CETP mice, a model for familial dysbetalipoproteinemia (FD). Mice were fed a western-type diet containing cholesterol without or with niacin (120 mg/kg/day), simvastatin (36 mg/kg/day) or their combination for 18 weeks. Similarly as in FD patients, niacin reduced total cholesterol by -39% and triglycerides by −50%, (both P2 = 0.69, P2 = 0.20, P<0.001). Niacin decreases atherosclerosis development mainly by reducing nonHDL-cholesterol with modest HDL-cholesterol-raising and additional anti-inflammatory effects. The additive effect of niacin on top of simvastatin is mostly dependent on its nonHDL-cholesterol-lowering capacities. These data suggest that clinical beneficial effects of niacin are largely dependent on its ability to lower LDL-cholesterol on top of concomitant lipid-lowering therapy.Keywords
This publication has 47 references indexed in Scilit:
- HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatmentEuropean Heart Journal, 2013
- The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: Baseline characteristics of study participants. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH) trialAmerican Heart Journal, 2011
- Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cellsJCI Insight, 2011
- Fenofibrate Increases Very Low Density Lipoprotein Triglyceride Production Despite Reducing Plasma Triglyceride Levels in APOE*3-Leiden.CETP MicePublished by Elsevier BV ,2010
- Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosisAtherosclerosis, 2010
- Anti-inflammatory effects of nicotinic acid in adipocytes demonstrated by suppression of fractalkine, RANTES, and MCP-1 and upregulation of adiponectinAtherosclerosis, 2010
- The dual PPARα/γ agonist tesaglitazar blocks progression of pre‐existing atherosclerosis in APOE*3Leiden.CETP transgenic miceBritish Journal of Pharmacology, 2009
- Extended-Release Niacin Alters the Metabolism of Plasma Apolipoprotein (Apo) A-I and ApoB-Containing LipoproteinsArteriosclerosis, Thrombosis, and Vascular Biology, 2008
- Gender-Related Differences in Electrocardiographic Parameters and Their Association With Cardiac Events in Patients After Myocardial InfarctionThe American Journal of Cardiology, 2008
- Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: a combined transcriptomics and metabolomics analysisGenome Biology, 2007