title: Niacin Promotes Cardiac Healing after Myocardial Infarction through Activation of the Myeloid Prostaglandin D2Receptor 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 PGD2receptor 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 PGD2release 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.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China (D.K., Y.S., Y.Y.); Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China (D.K., G.L., S.Z., B.T., Y.Y.); Department of Gastroenterology (J.L.), and Department of Cardiology (A.L.); Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; The Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu, China (Y.J.); International Institute for Integrative, Sleep Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan (M.L.); and Department of Veterans Affairs, Tennessee Valley Health Authority, and Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee (R.M.B.).
authors.forename: Deping
authors.initials: D
authors.lastname: Kong
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China (D.K., Y.S., Y.Y.); Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China (D.K., G.L., S.Z., B.T., Y.Y.); Department of Gastroenterology (J.L.), and Department of Cardiology (A.L.); Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; The Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu, China (Y.J.); International Institute for Integrative, Sleep Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan (M.L.); and Department of Veterans Affairs, Tennessee Valley Health Authority, and Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee (R.M.B.).
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China (D.K., Y.S., Y.Y.); Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China (D.K., G.L., S.Z., B.T., Y.Y.); Department of Gastroenterology (J.L.), and Department of Cardiology (A.L.); Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; The Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu, China (Y.J.); International Institute for Integrative, Sleep Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan (M.L.); and Department of Veterans Affairs, Tennessee Valley Health Authority, and Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee (R.M.B.).
authors.forename: Yujun
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China (D.K., Y.S., Y.Y.); Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China (D.K., G.L., S.Z., B.T., Y.Y.); Department of Gastroenterology (J.L.), and Department of Cardiology (A.L.); Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; The Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu, China (Y.J.); International Institute for Integrative, Sleep Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan (M.L.); and Department of Veterans Affairs, Tennessee Valley Health Authority, and Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee (R.M.B.).
authors.forename: Guizhu
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China (D.K., Y.S., Y.Y.); Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China (D.K., G.L., S.Z., B.T., Y.Y.); Department of Gastroenterology (J.L.), and Department of Cardiology (A.L.); Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; The Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu, China (Y.J.); International Institute for Integrative, Sleep Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan (M.L.); and Department of Veterans Affairs, Tennessee Valley Health Authority, and Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee (R.M.B.).
authors.forename: Shengkai
authors.initials: S
authors.lastname: Zuo
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China (D.K., Y.S., Y.Y.); Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China (D.K., G.L., S.Z., B.T., Y.Y.); Department of Gastroenterology (J.L.), and Department of Cardiology (A.L.); Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; The Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu, China (Y.J.); International Institute for Integrative, Sleep Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan (M.L.); and Department of Veterans Affairs, Tennessee Valley Health Authority, and Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee (R.M.B.).
authors.forename: Bo
authors.initials: B
authors.lastname: Tao
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China (D.K., Y.S., Y.Y.); Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China (D.K., G.L., S.Z., B.T., Y.Y.); Department of Gastroenterology (J.L.), and Department of Cardiology (A.L.); Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; The Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu, China (Y.J.); International Institute for Integrative, Sleep Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan (M.L.); and Department of Veterans Affairs, Tennessee Valley Health Authority, and Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee (R.M.B.).
authors.forename: Yong
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China (D.K., Y.S., Y.Y.); Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China (D.K., G.L., S.Z., B.T., Y.Y.); Department of Gastroenterology (J.L.), and Department of Cardiology (A.L.); Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; The Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu, China (Y.J.); International Institute for Integrative, Sleep Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan (M.L.); and Department of Veterans Affairs, Tennessee Valley Health Authority, and Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee (R.M.B.).
authors.forename: Ankang
authors.initials: A
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China (D.K., Y.S., Y.Y.); Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China (D.K., G.L., S.Z., B.T., Y.Y.); Department of Gastroenterology (J.L.), and Department of Cardiology (A.L.); Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; The Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu, China (Y.J.); International Institute for Integrative, Sleep Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan (M.L.); and Department of Veterans Affairs, Tennessee Valley Health Authority, and Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee (R.M.B.).
authors.forename: Michael
authors.initials: M
authors.lastname: Lazarus
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China (D.K., Y.S., Y.Y.); Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China (D.K., G.L., S.Z., B.T., Y.Y.); Department of Gastroenterology (J.L.), and Department of Cardiology (A.L.); Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; The Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu, China (Y.J.); International Institute for Integrative, Sleep Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan (M.L.); and Department of Veterans Affairs, Tennessee Valley Health Authority, and Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee (R.M.B.).
authors.forename: Richard M
authors.initials: RM
authors.lastname: Breyer
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China (D.K., Y.S., Y.Y.); Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China (D.K., G.L., S.Z., B.T., Y.Y.); Department of Gastroenterology (J.L.), and Department of Cardiology (A.L.); Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; The Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu, China (Y.J.); International Institute for Integrative, Sleep Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan (M.L.); and Department of Veterans Affairs, Tennessee Valley Health Authority, and Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee (R.M.B.) yuying@sibs.ac.cn yuying@tmu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009525:Niacin / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D007211:Indoles; C518174:MK-0524; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D014803:Vitamin B Complex; D009525:Niacin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor