title: Cardiomyocyte-specific overexpression of NO synthase-3 protects against myocardial ischemia-reperfusion injury.
abstract: OBJECTIVE
  The protective effect of NO synthase-3 (eNOS)-derived NO in limiting myocardial ischemia-reperfusion (MI-R) injury is well established. We reported previously that systemic genetic overexpression of eNOS attenuates MI-R injury. The purpose of the current study was to investigate tissue-specific genetic overexpression of the human eNOS gene.
  
  
  RESULTS
  To accomplish this, we used 2 distinct murine models of transgenic overexpression, a cardiomyocyte-specific eNOS overexpresser (CS eNOS-Tg) under the control of the alpha-myosin heavy chain promoter, and a systemic eNOS transgenic mouse (SYS eNOS-Tg) under control of the native eNOS promoter with an upstream endothelial enhancer element. Mice were subjected to 30 or 45 minutes of left coronary artery ischemia and 24 or 72 hours of reperfusion. CS eNOS-Tg mice displayed significantly decreased infarct size beyond that of mice with systemic overexpression. Additionally, CS eNOS-Tg mice exhibited better preservation of cardiac function compared with SYS eNOS-Tg mice after myocardial infarction.
  
  
  CONCLUSIONS
  These results provide evidence that site-specific targeting of eNOS gene therapy may be more advantageous in limiting MI-R injury and subsequent cardiac dysfunction.
authors.affiliation: Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Elrod
authors.forename: James J M
authors.initials: JJ
authors.lastname: Greer
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Bryan
authors.forename: Will
authors.initials: W
authors.lastname: Langston
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Szot
authors.forename: Henock
authors.initials: H
authors.lastname: Gebregzlabher
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
authors.forename: Martin
authors.initials: M
authors.lastname: Feelisch
authors.forename: David J
authors.initials: DJ
authors.lastname: Lefer
mesh_terms: D000818:Animals; D004452:Echocardiography; D018390:Gene Targeting; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III