RT Journal Article
SR Electronic
T1 Niacin promotes cardiac healing after myocardial infarction through activation of the myeloid prostaglandin D2 receptor subtype 1
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.116.238261
DO 10.1124/jpet.116.238261
A1 Deping Kong
A1 Juanjuan Li
A1 Yujun Shen
A1 Guihu Liu
A1 Shengkai Zuo
A1 Bo Tao
A1 Yong Ji
A1 Ankang Lu
A1 Michael Lazarus
A1 Richard M Breyer
A1 Ying Yu
YR 2017
UL http://jpet.aspetjournals.org/content/early/2017/01/06/jpet.116.238261.abstract
AB Niacin is a well-established drug used to lower cholesterol and prevent cardiovascular disease (CVD) events. However, niacin also causes cutaneous flushing side effects due to release of the proresolution mediator prostaglandin (PG) D2. Recent randomized clinical trials have demonstrated that addition of niacin with laropiprant (a PGD2 receptor subtype 1 [DP1] blocker) to statin-based therapies does not significantly decrease the risk of CVD events but increases the risk of serious adverse events. Here, we tested whether, and how, niacin beneficial effects in vivo myocardial ischemia requires the activation of the PGD2/DP1 axis. Here we try to test whether niacin facilitates cardiac recovery from myocardial infarction (MI) through activation of the PGD2/DP1 axis. Myocardial infarction (MI) was reproduced by ligation of the left anterior descending branch of the coronary artery in mice. We found that niacin increased PGD2 release in macrophages and shifted macrophages to M2 polarization both in vitro and in vivo by activation of DP1 and accelerated inflammation resolution in zymosan-induced peritonitis in mice. Moreover, niacin treatment facilitated wound healing and improved cardiac function after MI through DP1-mediated M2 bias and timely resolution of inflammation in infarcted hearts. In addition, we found that niacin intake also stimulated M2 polarization of peripheral monocytes in humans. Collectively, niacin promoted cardiac functional recovery after ischemic myocardial infarction through DP1-mediated M2 polarization and timely resolution of inflammation in hearts. These results indicated that DP1 inhibition may attenuate the cardiovascular benefits of niacin.