title: Paeoniflorin protects diabetic mice against myocardial ischemic injury via the transient receptor potential vanilloid 1/calcitonin gene-related peptide pathway.
abstract: BACKGROUND
  Diabetes mellitus has multiple complications including neuropathy and increases cardiovascular events. Paeoniflorin (PF), a monoterpene glycoside, plays an essential role in neuroprotection and ischemic heart disease. In this study, we aimed to investigate the hypothesis that PF protects mice with diabetes mellitus against myocardial ischemic injury, and determine its associated mechanisms.
  
  
  RESULTS
  Myocardial infarction (MI) was generated in the streptozotocin-mediated diabetic mice, which were pretreated with either vehicle or PF, respectively. Myocardial infarct size, myocardial enzyme, cardiac function, circulating calcitonin gene-related peptide (CGRP) concentration, histological analysis and the expression of associated molecules were determined and compared among different experimental groups. Compared to diabetic hearts pretreated with vehicle, hearts pretreated with PF exhibited less tissue damage and better CGRP concentration in serum when subjected to myocardial ischemia. Transient receptor potential vanilloid 1(TRPV1) gene knockout attenuated PF-mediated cardioprotection. Moreover, a specific Ca(2+)/calmodulin-dependent protein kinase (CaMK) inhibitor, KN-93, increased tissue damage and decreased CGRP activity in serum. Meanwhile, pretreated with PF increased the phosphorylation of cAMP response element binding protein (CREB).
  
  
  CONCLUSIONS
  Taken together, these findings demonstrate that PF protects diabetic mice against MI at least partially via the TRPV1/CaMK/CREB/CGRP signaling pathway.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003 China.
authors.forename: Fei
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003 China.
authors.forename: Dongchen
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003 China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003 China.
authors.forename: Zewei
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003 China.
authors.forename: Jie
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003 China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003 China.
authors.forename: Wengting
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003 China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003 China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003 China.
authors.forename: Liangrong
authors.initials: L
authors.lastname: Zheng
keywords: CGRP; Diabetes mellitus; Myocardial ischemia; Neuroprotection; Paeoniflorin; TRPV1