Up-regulation of calcitonin gene-related peptide protects streptozotocin-induced diabetic hearts from ischemia/reperfusion injury

Abstract

BackgroundDiabetic hearts are vulnerable to ischemia/reperfusion (I/R) injury. Pretreatment with exogenous calcitonin gene-related peptide (CGRP) exerts a cardioprotective effect against myocardial I/R injury. Our previous study found that the CGRP level was decreased in diabetic hearts. This study aimed to investigate whether up-regulation of CGRP could reduce I/R injury in diabetic hearts. Methods and resultsAdenovirus encoding the CGRP gene (Ad-CGRP) was injected intramyocardially in mice with or without streptozotocin (STZ) treatment. Three days after injection, the hearts were subjected to in vivo and in vitro I/R. Myocardial infarct size, cardiac function, lactate dehydrogenase (LDH) level in plasma and effluents, and cell mitochondrial function were measured. After ischemia (30min) and reperfusion (24h) in vivo, diabetes mellitus (DM) mice had greater myocardial infarct size than their nondiabetic counterparts, and released more LDH in plasma. However, CGRP gene transfer reduced myocardial infarct size and plasma LDH level in both non-DM and DM hearts. After 30min global ischemia and 40min reperfusion in vitro, the DM hearts demonstrated increased left ventricular end-diastolic pressure (LVEDP) and effluent LDH level, and decreased left ventricular developed pressure (LVDP), coronary flow (CF), as well as cell mitochondrial function, when compared with the non-DM hearts. Again, CGRP gene transfer could protect against I/R injury in both non-DM and DM hearts. ConclusionsAdenovirus-mediated up-regulation of CGRP gene expression protects diabetic hearts against I/R injury.