Intracoronary, adenovirus-mediated Akt gene transfer in heart limits infarct size following ischemia-reperfusion injury in vivo

Wenfeng Miao, Zhengyu Luo, Richard N. Kitsis, Kenneth Walsh

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Background: Previous data have shown that enhanced Akt signaling inhibits cardiac myocyte apoptosis in vitro and in vivo. To elucidate the contribution of apoptosis to the pathogenesis of the infarct, we investigated whether intra-coronary Akt gene delivery could reduce gross infarct size following ischemia/reperfusion injury. Methods and Results: Replication-defective adenoviral constructs encoding a myristoylated, constitutively-active form of Akt (myrAkt) or β-galactosidase were delivered to rat hearts by intracoronary perfusion. Twenty-four h after gene transduction, hearts in both groups underwent 45 min of ischemia followed by 4h of reperfusion. A third group of animals also underwent ischemia-reperfusion injury but were not transduced with an adenoviral vector. The proportion of the left ventricle at risk was not different among the experimental groups. However, infarct size as a proportion of the area at risk was significantly lower in myrAkttreated group than in the β-galactosidase treated group or in the control group that was not subject to intracoronary perfusion (myrAkt = 20.9 ± 2.7% v β-galactosidase = 56.1 ± 3.9% and control = 46.2 ± 4.6%. P<0,05), as was infarct size as a proportion of the total left ventricle (myrAkt = 11.4 ± 3.2 v β-galactosidase = 32.9 ± 3.3 and control = 23.5 ± 3.0, P<0.05). Conclusions: These data demonstrate that Akt signaling limits infarct size following ischemia/reperfusion injury and they indicate that the activation of this pathway may be useful in protecting against myocardial loss in the diseased heart.

Original languageEnglish (US)
Pages (from-to)2397-2402
Number of pages6
JournalJournal of Molecular and Cellular Cardiology
Volume32
Issue number12
DOIs
StatePublished - Jan 1 2000

Keywords

  • Akt
  • Apoptosis
  • Area at risk
  • Infarct
  • Ischemia
  • Myocytes
  • Reperfusion

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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