Yoshiyuki Kataoka1, Rei Shibata2, Koji Ohashi3, Takahiro Kambara1, Takashi Enomoto3, Yusuke Uemura1, Yasuhiro Ogura1, Daisuke Yuasa1, Kazuhiro Matsuo1, Takanobu Nagata4, Toyoharu Oba4, Hideo Yasukawa4, Yasushi Numaguchi1, Takahito Sone5, Toyoaki Murohara1, Noriyuki Ouchi6. 1. Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. 2. Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: rshibata@med.nagoya-u.ac.jp. 3. Department of Molecular Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. 4. Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. 5. Department of Cardiology, Ogaki Municipal Hospital, Minaminokawa, Ogaki, Japan. 6. Department of Molecular Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: nouchi@med.nagoya-u.ac.jp.
Abstract
OBJECTIVES: This study examined the impact of omentin on myocardial injury in a mouse model of ischemia/reperfusion (I/R) and explored its underlying mechanisms. BACKGROUND: Obesity is a major risk factor for ischemic heart disease. Omentin is a circulating adipokine that is down-regulated by obesity. METHODS: In patients who underwent successful reperfusion treatment after acute myocardial infarction, cardiac function and perfusion defect were assessed by using scintigraphic images. Mice were subjected to myocardial ischemia followed by reperfusion. RESULTS: This study found that high levels of plasma omentin were associated with improvement of heart damage and function after reperfusion therapy in patients with acute myocardial infarction. Systemic administration of human omentin to mice led to a reduction in myocardial infarct size and apoptosis after I/R, which was accompanied by enhanced phosphorylation of AMP-activated protein kinase (AMPK) and Akt in the ischemic heart. Fat-specific overexpression of human omentin also resulted in reduction of infarct size after I/R. Blockade of AMPK or Akt activity reversed omentin-induced inhibition of myocardial ischemic damage and apoptosis in mice. In cultured cardiomyocytes, omentin suppressed hypoxia/reoxygenation-induced apoptosis, which was blocked by inactivation of AMPK or Akt. CONCLUSIONS: Our data indicate that omentin functions as an adipokine that ameliorates acute ischemic injury in the heart by suppressing myocyte apoptosis through both AMPK- and Akt-dependent mechanisms.
OBJECTIVES: This study examined the impact of omentin on myocardial injury in a mouse model of ischemia/reperfusion (I/R) and explored its underlying mechanisms. BACKGROUND:Obesity is a major risk factor for ischemic heart disease. Omentin is a circulating adipokine that is down-regulated by obesity. METHODS: In patients who underwent successful reperfusion treatment after acute myocardial infarction, cardiac function and perfusion defect were assessed by using scintigraphic images. Mice were subjected to myocardial ischemia followed by reperfusion. RESULTS: This study found that high levels of plasma omentin were associated with improvement of heart damage and function after reperfusion therapy in patients with acute myocardial infarction. Systemic administration of humanomentin to mice led to a reduction in myocardial infarct size and apoptosis after I/R, which was accompanied by enhanced phosphorylation of AMP-activated protein kinase (AMPK) and Akt in the ischemic heart. Fat-specific overexpression of humanomentin also resulted in reduction of infarct size after I/R. Blockade of AMPK or Akt activity reversed omentin-induced inhibition of myocardial ischemic damage and apoptosis in mice. In cultured cardiomyocytes, omentin suppressed hypoxia/reoxygenation-induced apoptosis, which was blocked by inactivation of AMPK or Akt. CONCLUSIONS: Our data indicate that omentin functions as an adipokine that ameliorates acute ischemic injury in the heart by suppressing myocyte apoptosis through both AMPK- and Akt-dependent mechanisms.
Authors: Sarah R Anthony; Adrienne R Guarnieri; Anamarie Gozdiff; Robert N Helsley; Albert Phillip Owens; Michael Tranter Journal: Clin Sci (Lond) Date: 2019-11-29 Impact factor: 6.124
Authors: Jochen D Muehlschlegel; Danos C Christodoulou; David McKean; Joshua Gorham; Erica Mazaika; Mahyar Heydarpour; Grace Lee; Steven R DePalma; Tjorvi E Perry; Amanda A Fox; Stanton K Shernan; Christine E Seidman; Sary F Aranki; Jon G Seidman; Simon C Body Journal: Anesthesiology Date: 2015-03 Impact factor: 7.892