Abstract
Niacin is a well established drug used to lower cholesterol and prevent cardiovascular disease events. However, niacin also causes cutaneous flushing side effects due to release of the proresolution mediator prostaglandin D2 (PGD2). 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 cardiovascular disease events, but increases the risk of serious adverse events. Here, we tested whether, and how, niacin beneficial effects on myocardial ischemia require the 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.
Footnotes
- Received October 10, 2016.
- Accepted December 30, 2016.
This work was supported by the National Natural Science Foundation of China [Grants 81525004, 91439204, 31200860, and 91639302], Shanghai Committee of Science and Technology Key Program [Grants 14JC1407400, 15140902000], Science and Technology Service Network Initiative [Grant KFJ-EW-STS-099], Postdoctoral Fellowship Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences [Grants 2012KIP514 and 2013KIP312], and the National Institutes of Health [Grants GM15431 and DK37097], as well as a Merit Award from the Department of Veterans Affairs, Vanderbilt University [1BX000616]. Y.J. and Y.Y. are Fellows at the Jiangsu Collaborative Innovation Center for Cardiovascular Disease Translational Medicine.
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- Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics
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