Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice.
Heme oxygenase (HO)-1 degrades the pro-oxidant heme and generates carbon monoxide and antioxidant bilirubin. We have previously shown that in response to hypoxia, HO-1-null mice develop infarcts in the right ventricle of their hearts and that their cardiomyocytes are damaged by oxidative stress. To test whether HO-1 protects against oxidative injury in the heart, we generated cardiac-specific transgenic mice overexpressing different levels of HO-1. By use of a Langendorff preparation, hearts from transgenic mice showed improved recovery of contractile performance during reperfusion after ischemia in an HO-1 dose-dependent manner. In vivo, myocardial ischemia and reperfusion experiments showed that infarct size was only 14.7% of the area at risk in transgenic mice compared with 56.5% in wild-type mice. Hearts from these transgenic animals had reduced inflammatory cell infiltration and oxidative damage. Our data demonstrate that overexpression of HO-1 in the cardiomyocyte protects against ischemia and reperfusion injury, thus improving the recovery of cardiac function.
Yet
S F
SF
Cardiovascular and Pulmonary and Critical Care, Division and the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. syet@rics.bwh.harvard.edu.
Tian
R
R
Layne
M D
MD
Wang
Z Y
ZY
Maemura
K
K
Solovyeva
M
M
Ith
B
B
Melo
L G
LG
Zhang
L
L
Ingwall
J S
JS
Dzau
V J
VJ
Lee
M E
ME
Perrella
M A
MA
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005838:Genotype; D006321:Heart / Q000503:physiopathology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics* / Q000378:metabolism; D051547:Heme Oxygenase-1; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000201:enzymology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology*
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse