Niacin Promotes Cardiac Healing after Myocardial Infarction through Activation of the Myeloid Prostaglandin D2 Receptor Subtype 1.

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.

• Authors: Deping Kong, Juanjuan Li, Yujun Shen, Guizhu Liu, Shengkai Zuo, Bo Tao, Yong Ji, Ankang Lu, Michael Lazarus, Richard M Breyer, Ying Yu
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 360 Issue 3 Pg. 435-444 (03 2017) ISSN: 1521-0103 [Electronic] United States
• PMID: 28057839 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Chemical References

• Indoles
• MK-0524
• Receptors, Immunologic
• Receptors, Prostaglandin
• Vitamin B Complex
• Niacin
• Prostaglandin D2
• prostaglandin D2 receptor

Topics

• Animals
• Disease Models, Animal
• Indoles (administration & dosage, adverse effects)
• Inflammation (drug therapy, metabolism)
• Mice
• Myocardial Infarction (drug therapy, metabolism, physiopathology)
• Myocardium (metabolism, pathology)
• Niacin (pharmacology)
• Prostaglandin D2 (metabolism)
• Receptors, Immunologic (metabolism)
• Receptors, Prostaglandin (metabolism)
• Regeneration (drug effects, physiology)
• Treatment Outcome
• Vitamin B Complex (pharmacology)