title: Impact of cardiac-specific expression of CD39 on myocardial infarct size in mice.
abstract: OBJECTIVE
  Prior work suggests that ischemic preconditioning increases the level of CD39 in the heart and contributes to cardiac protection. Therefore, we examined if targeted cardiac expression of CD39 protects against myocardial injury.
  
  
  METHODS
  Mice with cardiac-specific expression of human CD39 (αMHC/hCD39-Tg) were generated, characterized and subjected to left coronary artery ischemia-reperfusion injury and infarct size at 24h following injury quantified.
  
  
  RESULTS
  αMHC/hCD39-Tg mice have increased in cardiac ATPase and ADPase activity compared to WT littermates. The increased activity in αMHC/hCD39-mice was inhibited by the CD39 antagonist sodium polyoxotungstate (POM-1). Measurement of basal cardiac function by echocardiography revealed that αMHC/hCD39-Tg mice have a lower resting heart rate and increased stroke volume. In response to myocardial ischemia, systolic and diastolic function was better preserved in αMHC/hCD39-Tg compared to WT mice. Comparison of Tau also revealed preserved cardiac relaxation during ischemia in αMHC/hCD39-Tg hearts. Assessment of myocardial infarct size in response to 60min of ischemia and 24h of reperfusion demonstrated a significant reduction in infarct size in αMHC/hCD39-Tg hearts. Analysis of isolated cardiomyocytes revealed no basal difference in calcium transients between WT and αMHC/hCD39-Tg cardiomyocytes. However, in response to isoproterenol stimulation, there was a trend toward lower calcium transients in αMHC/hCD39 cardiomyocytes suggesting less calcium accumulation in response to metabolic stress.
  
  
  CONCLUSIONS
  Cardiac-specific expression of CD39 reduces myocardial dysfunction and infarct size following ischemia-reperfusion injury. Increasing nucleotidase expression in the heart may be a novel approach to protect the heart from ischemic injury.
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Smith
authors.affiliation: Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Zhaobin
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Novitskaya
authors.affiliation: Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Chepurko
authors.affiliation: Department of Neuroscience, The Ohio State University, Columbus, OH, USA.
authors.forename: Xin-An
authors.initials: XA
authors.lastname: Pu
authors.affiliation: Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Debra G
authors.initials: DG
authors.lastname: Wheeler
authors.affiliation: Department of Physiology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Ziolo
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA; Department of Pharmacology, Vanderbilt University, Nashville, TN, USA; Department of Pathology, Immunology and Microbiology, Vanderbilt University, Nashville, TN, USA. Electronic address: richard.gumina@vanderbilt.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gumina
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001081:Apyrase / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography; D015870:Gene Expression; D006339:Heart Rate / Q000235:genetics; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics; D013318:Stroke Volume / Q000235:genetics
chemical_list: D015703:Antigens, CD; D001081:Apyrase; C067869:CD39 antigen; D007545:Isoproterenol; D002118:Calcium
keywords: CD39; Infarct; Ischemia-reperfusion