Journal
JOURNAL OF DIABETES AND ITS COMPLICATIONS
Volume 29, Issue 3, Pages 323-328Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jdiacomp.2015.01.006
Keywords
Heart disease; Reperfusion injury; Type 2 diabetes mellitus; Nerve growth factor; TRPV1 protein; Mouse
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Funding
- International Collaboration Project of Science and Technology Department of Zhejiang Province [2011C14027]
- National Natural Science Foundation of China [81170167, 30801213, 81400277, 81200191]
- foundation from Zhejiang Provincial Administration of Traditional Chinese Medicine [2011ZQ013]
- Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents
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Aims: Nerve growth factor (NGF), a member of the neurotrophin family, plays an essential role in diabetic neuropathy and ischemic heart disease. In the present study, we explored the potential role of NGF and the involvement of TRPV1 receptor in isolated diabetic mouse hearts following ischemia/reperfusion (I/R) injury. Methods: Adenovirus-mediated NGF gene delivery was performed on diabetic and sham hearts 8 weeks after streptozotocin treatment. The sciatic nerve conduction velocity was recorded using a biological signal acquisition system. Forty-eight hours after heart surgery, mice were subjected to I/R injury using a Langendorff system. Several cardiac parameters and the expression of associated molecules were analyzed during the experiment. Results: The sciatic nerve conduction velocity was reduced in diabetic mice compared with that in control mice. Decreased expression of NGF, TRPV1, and the downstream neurotransmitters CGRP and SP was observed in the diabetic hearts. Adenovirus-mediated NGF overexpression reversed the reduction in TRPV1 and downstream neuropeptides, resulting in improved cardiac recovery post-I/R injury in diabetic hearts. The protective effect of NGF was abolished by CGRP8-37 (a selective CGRP antagonist), while it was preserved by low-dose capsaicin. Conclusions: The NGF-induced up-regulation of TRPV1 via the increased synthesis and release of endogenous CGRP leads to improved cardiac performance in I/R-injured diabetic heart. (C) 2015 Elsevier Inc. All rights reserved.
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