title: Up-regulation of calcitonin gene-related peptide protects streptozotocin-induced diabetic hearts from ischemia/reperfusion injury.
abstract: BACKGROUND
  Diabetic 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.
  
  
  RESULTS
  Adenovirus 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 (30 min) 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 30 min global ischemia and 40 min 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.
  
  
  CONCLUSIONS
  Adenovirus-mediated up-regulation of CGRP gene expression protects diabetic hearts against I/R injury.
authors.affiliation: Department of Cardiovascular Sciences, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Liang-rong
authors.initials: LR
authors.lastname: Zheng
authors.forename: Jie
authors.initials: J
authors.lastname: Han
authors.forename: Lei
authors.initials: L
authors.lastname: Yao
authors.forename: Yi-Lan
authors.initials: YL
authors.lastname: Sun
authors.forename: Dong-mei
authors.initials: DM
authors.lastname: Jiang
authors.forename: Shen-jiang
authors.initials: SJ
authors.lastname: Hu
authors.forename: Lei
authors.initials: L
authors.lastname: Shao
authors.forename: Zhi-hui
authors.initials: ZH
authors.lastname: Sun
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Wang
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000235:genetics; D002316:Cardiotonic Agents / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D018014:Gene Transfer Techniques; D006321:Heart; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D011897:Random Allocation; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D002316:Cardiotonic Agents; D015740:Calcitonin Gene-Related Peptide