Protection against myocardial ischemia/reperfusion injury by short-term diabetes: Enhancement of VEGF formation, capillary density, and activation of cell survival signaling

Guochuan Ma, Mohamed Al-Shabrawey, John A. Johnson, Rahul Datar, Huda E. Tawfik, Dehuang Guo, Ruth B. Caldwell, R. William Caldwell

Research output: Contribution to journalArticle

50 Scopus citations


The aims of this study were to determine effects of diabetes duration on myocardial ischemia/reperfusion (I/R) injury and test whether time-dependent differences in sensitivity of the streptozotocin diabetic rat heart to I/R are related to differences in vascular density, levels of vascular endothelial growth factor (VEGF) or endothelial nitric oxide synthase (eNOS) expression, NO formation, activation of Akt, and/or oxidative stress. After 2 or 6 weeks of streptozotocin-induced diabetes, I/R injury was induced by occlusion (30 min) and reperfusion of the left descending coronary artery. After 2 weeks of diabetes, infarct size and cleavage of caspase-3, a proapoptosis signal, were decreased as compared with normoglycemic controls or rats that had been diabetic for 6 weeks, whereas capillary density and levels of VEGF and eNOS protein and cardiac NOx levels were all increased. Phosphorylation of Akt, a prosurvival signal, was also significantly increased after 2 weeks of diabetes. Cardiac lipid peroxidation was comparable to controls after 2 weeks of diabetes, whereas levels of nitrotyrosine, a peroxynitrite biomarker, were reduced. After 6 weeks of diabetes, lipid peroxidation was increased and levels of VEGF and plasma NO were reduced as compared with controls or rats diabetic for 2 weeks. Our results indicate endogenous cardioprotective mechanisms become transiently activated in this early stage of diabetes and that this may protect the heart from I/R injury through enhancement of VEGF and eNOS expression, NO formation, activation of cell survival signals, and decreased oxidative stress.

Original languageEnglish (US)
Pages (from-to)415-427
Number of pages13
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Issue number6
StatePublished - Sep 1 2006



  • Diabetes
  • Heart
  • Ischemia/reperfusion
  • Oxidative stress
  • Preconditioning
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Pharmacology

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