Niacin Reduces Atherosclerosis Development in APOE3Leiden.CETP Mice Mainly by Reducing NonHDL-Cholesterol

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 effec...

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Bibliographic Details
Published in:PloS one 2013-06, Vol.8 (6), p.e66467
Main Authors: Kühnast, Susan, Louwe, Mieke C, Heemskerk, Mattijs M, Pieterman, Elsbet J, van Klinken, Jan B, van den Berg, Sjoerd A A, Smit, Johannes W A, Havekes, Louis M, Rensen, Patrick C N, van der Hoorn, José W A, Princen, Hans M G, Jukema, J Wouter
Format: Article
Language:English
Subjects:
Acids
Animals
Aorta
Apolipoprotein E
Apolipoprotein E3 - genetics
Apolipoproteins
Arteriosclerosis
Atherosclerosis
Atherosclerosis - prevention & control
Biological Transport
Biology
Blood cholesterol
Cardiology
Cardiovascular disease
Cholesterol
Cholesterol - blood
Cholesterol Ester Transfer Proteins - genetics
Clinical trials
Collagen
Endocrinology
Endothelium
Female
Gene Expression - drug effects
High density lipoprotein
Inflammation
Laboratories
Lesions
Lipids
Lipoproteins (very low density)
Liver - drug effects
Liver - metabolism
Low density lipoprotein
Low density lipoproteins
Lymphocytes
Lymphocytes T
Macrophages
Mathematics
Medical research
Medicine
Metabolic disorders
Mice
Mice, Transgenic
Monocytes
Niacin
Niacin - pharmacology
Plasma
RNA, Messenger - genetics
Rodents
Simvastatin
Simvastatin - pharmacology
Statins
T cells
Triglycerides
Triglycerides - blood
Vitamin B
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Summary: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 P
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0066467