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论文题目: Niacin Promotes Cardiac Healing after Myocardial Infarction through Activation of the Myeloid Prostaglandin D-2 Receptor Subtype 1
英文论文题目: Niacin Promotes Cardiac Healing after Myocardial Infarction through Activation of the Myeloid Prostaglandin D-2 Receptor Subtype 1
第一作者: Kong, DP; Li, JJ; Shen, YJ; Liu, GZ; Zuo, SK; Tao, B; Ji, Y; Lu, AK; Lazarus, M; Breyer, RM; Yu, Y
英文第一作者: Kong, DP; Li, JJ; Shen, YJ; Liu, GZ; Zuo, SK; Tao, B; Ji, Y; Lu, AK; Lazarus, M; Breyer, RM; Yu, Y
联系作者: Yu, Y (reprint author), Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, 294 Taiyuan Rd, Shanghai 200031, Peoples R China.
英文联系作者: Yu, Y (reprint author), Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, 294 Taiyuan Rd, Shanghai 200031, Peoples R China.
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发表年度: 2017
卷: 360
期: 3
页码: 435-444
摘要: 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 D-2 (PGD(2)). 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 PGD(2)/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 PGD(2) 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.
英文摘要: 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 D-2 (PGD(2)). 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 PGD(2)/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 PGD(2) 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.
刊物名称: JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
英文刊物名称: JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
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学科: Pharmacology & Pharmacy
英文学科: Pharmacology & Pharmacy
影响因子: 3.867
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论文类别: Article
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