Transient Receptor Potential Vanilloid 1 Regulates Mitochondrial Membrane Potential and Myocardial Reperfusion Injury

Transient Receptor Potential Vanilloid 1 Regulates Mitochondrial Membrane Potential and Myocardial Reperfusion Injury

Background The transient receptor potential vanilloid 1 (TRPV1) mediates cellular responses to pain, heat, or noxious stimuli by calcium influx; however, the cellular localization and function of TRPV1 in the cardiomyocyte is largely unknown. We studied whether myocardial injury is regulated by TRPV...

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Bibliographic Details
Published in:Journal of the American Heart Association 2016-09, Vol.5 (9), p.n/a
Main Authors: Hurt, Carl M., Lu, Yao, M. Stary, Creed, Piplani, Honit, Small, Bryce A., Urban, Travis J., Qvit, Nir, Gross, Garrett J., Mochly‐Rosen, Daria, Gross, Eric R.
Format: Article
Language:eng
Subjects:
acute myocardial infarction
calcineurin
cyclosporine
infarct size
ischemia
mitochondria
Original Research
reperfusion
reperfusion injury
transient receptor potential vanilloid 1
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Summary:Background The transient receptor potential vanilloid 1 (TRPV1) mediates cellular responses to pain, heat, or noxious stimuli by calcium influx; however, the cellular localization and function of TRPV1 in the cardiomyocyte is largely unknown. We studied whether myocardial injury is regulated by TRPV1 and whether we could mitigate reperfusion injury by limiting the calcineurin interaction with TRPV1. Methods and Results In primary cardiomyocytes, confocal and electron microscopy demonstrates that TRPV1 is localized to the mitochondria. Capsaicin, the specific TRPV1 agonist, dose‐dependently reduced mitochondrial membrane potential and was blocked by the TRPV1 antagonist capsazepine or the calcineurin inhibitor cyclosporine. Using in silico analysis, we discovered an interaction site for TRPV1 with calcineurin. We synthesized a peptide, V1‐cal, to inhibit the interaction between TRPV1 and calcineurin. In an in vivo rat myocardial infarction model, V1‐cal given just prior to reperfusion substantially mitigated myocardial infarct size compared with vehicle, capsaicin, or cyclosporine (24±3% versus 61±2%, 45±1%, and 49±2%, respectively; n=6 per group; P
ISSN:2047-9980
2047-9980