UNVEILING NOVEL CARDIOPROTECTIVE EFFECTS OF GYY4137, A SLOW-RELEASING HYDROGEN SULFIDE DONOR, AND THEIR RELATIONSHIP TO NEUROHORMONAL MODULATION AND MICRORNA PROFILES DURING MYOCARDIAL ISCHEMIC INJURY.

Hydrogen sulfide (H2S) is emerging as an important endogenous modulator in diverse physiological and pathophysiological events. Yet, its role on neurohormonal modulation and microRNA profiles during myocardial ischemic (MI) injury has not been clearly defined. This present study was designed to investigate the cardioprotective effects of slow-releasing water-soluble H2S donor GYY4137 (GYY) and their relationship to neurohormonal modulation and microRNA profiles during myocardial ischemic injury. In this study, it was found that treatment with GYY (100mg/kg/48hrs) significantly provided preservation of left ventricular (LV) dimensions and function 2 days and 7 days after MI comparable to healthy sham-operated rats. Histological and immunostaining showed that GYY had significantly less LV fibrosis and higher density of blood vessels in the LV scar area. Moreover, treatment with GYY increased levels of the natriuretic peptides ANP and BNP in association with enhanced cyclic GMP levels. In addition, GYY treatment had effect on the microRNA profiles. In conclusion, GYY preserves cardiac function, attenuates adverse remodeling and may exert post-ischemic cardioprotective (pro-angiogenic, anti-fibrotic) effects in part through enhanced early post-ischemic endogenous natriuretic peptide activation and possibly through microRNA modulation.

Author dc:creator

• SHERA LILYANNA

• GYY4137, microRNA, neurohormonal modulation, myocardial ischemic injury