Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 373, Issue 6, pp 415–427

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
Original Article

DOI: 10.1007/s00210-006-0102-1

Cite this article as:
Ma, G., Al-Shabrawey, M., Johnson, J.A. et al. Naunyn-Schmied Arch Pharmacol (2006) 373: 415. doi:10.1007/s00210-006-0102-1

Abstract

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.

Keywords

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

Abbreviations

AAR

area at risk

eNOS

Endothelial NO synthase

HR

heart rate

I/R

Ischemia/reperfusion

IS

infarct size

LV

left ventricular

MBP

mean blood pressure

MI

myocardial infarction

NO

Nitric oxide

NT

Nitrotyrosine

STZ

Streptozotocin

TTC

2,3,5-triphenyltetrazolium chloride

VEGF

Vascular endothelial growth factor

WC

Week control

WD

Week diabetes

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Guochuan Ma
    • 1
  • Mohamed Al-Shabrawey
    • 2
    • 3
  • John A. Johnson
    • 1
  • Rahul Datar
    • 1
  • Huda E. Tawfik
    • 1
  • Dehuang Guo
    • 1
  • Ruth B. Caldwell
    • 2
    • 3
    • 4
  • R. William Caldwell
    • 1
  1. 1.Department of Pharmacology & ToxicologyMedical College of GeorgiaAugustaUSA
  2. 2.Department of Cellular Biology & AnatomyMedical College of GeorgiaAugustaUSA
  3. 3.Department of OphthalmologyMedical College of GeorgiaAugustaUSA
  4. 4.Vascular Biology CenterMedical College of GeorgiaAugustaUSA

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