TY - JOUR
AU1 - Ma, Guochuan
AU2 - Al-Shabrawey, Mohamed
AU3 - Johnson, John
AU4 - Datar, Rahul
AU5 - Tawfik, Huda
AU6 - Guo, Dehuang
AU7 - Caldwell, Ruth
AU8 - Caldwell, R.
AB - 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.
TI - Protection against myocardial ischemia/reperfusion injury by short-term diabetes: enhancement of VEGF formation, capillary density, and activation of cell survival signaling
JF - Naunyn-Schmiedeberg's Archives of Pharmacology
DO - 10.1007/s00210-006-0102-1
DA - 2006-09-06
UR - https://www.deepdyve.com/lp/springer-journals/protection-against-myocardial-ischemia-reperfusion-injury-by-short-B62EVxLomS
SP - 415
EP - 427
VL - 373
IS - 6
DP - DeepDyve
ER -