Chromofungin, CgA47-66-derived peptide, produces basal cardiac effects and postconditioning cardioprotective action during ischemia/reperfusion injury

作者：Filice Elisabetta; Pasqua Teresa; Quintieri Anna Maria; Cantafio Patrizia; Scavello Francesco; Amodio Nicola; Cerra Maria Carmela; Marban Celine; Schneider Francis; Metz Boutigue Marie Helene; Angelone Tommaso^*

来源：Peptides, 2015, 71: 40-48.

DOI：10.1016/j.peptides.2015.06.013

• Chromogranins
• Chromofungin
• Nitric oxide
• Cardioprotection
• Intracellular pathways

Endogenous chromogranin A (CgA)-derived peptides are secreted by nervous, endocrine and immune cells. Chromofungin (Chr: CgA47-66) is one of these peptides that display antimicrobial activities and activate neutrophils, with important implications in inflammation and innate immunity. The aim of the present study is to examine the effects of Chr on isolated and Langendorff perfused rat hearts.
The study was performed by using the isolated and Langendorff perfused rat hearts, Elisa assay and real-time PCR.
We found that, under basal conditions, increasing doses (11-165 nM) of Chr induced negative inotropic effects without changing coronary pressure. This action was mediated by the AKT/eNOS/cGMP/PKG pathway. We also found that Chr acted as a postconditioning (PostC) agent against ischemia/reperfusion (I/R) damages, reducing infarct size and LDH level. Cardioprotection involved PI3K, RISK pathway, MitoKATP and miRNA-21.
We suggest that Chr directly affects heart performance, protects against I/R myocardial injuries through the activation of prosurvival kinases. Results may propose Chr as a new physiological neuroendocrine modulator able to prevent heart dysfunctions, also encouraging the clarification of its clinical potential.

• 出版日期2015-9