Pituitary adenylate cyclase-activating polypeptide attenuates coronary microembolization-induced myocardial apoptosis via PAC1 receptor activation in rats.

BACKGROUND

Coronary microembolization (CME) precipitates cardiac failure chiefly by provoking cardiomyocyte death. Pituitary adenylate cyclase-activating polypeptide (PACAP) displays pronounced cytoprotective actions across multiple cardiac insults through PAC1 engagement, yet its influence on CME-induced damage remains unexplored. We therefore examined whether PACAP curbs CME-provoked myocardial apoptosis via PAC1-dependent cascades.

METHODS

Animals were allocated to Sham, CME, CME + PACAP, CME + PACAP + PAC1 blocker (PACAP6-38), and CME + Ant (PAC1 antagonist alone) cohorts. CME was induced by intracoronary microsphere infusion. Evaluations encompassed systolic performance (echocardiography), injury severity (serum cTnI), apoptotic burden (TUNEL, cleaved caspase-3), and pathway proteins (Western blot, immunohistochemistry). Heart-weight-to-body-weight index and regression between apoptotic fraction and LVEF were additionally computed.

RESULTS

Relative to Sham, CME depressed contractility, raised cTnI, and expanded apoptosis. PACAP administration restored function, attenuated cTnI release, and blunted cell death-benefits nullified by PAC1 antagonism, which alone lacked effect. At the molecular level, PACAP enhanced the phosphorylation of Akt and Bad, elevated Bcl-2/Bax ratio, and curbed cytosolic cytochrome c in a PAC1-restricted manner. Apoptotic score inversely tracked LVEF; PAC1 abundance and HW/BW index remained uniform among groups.

CONCLUSION

PACAP counters CME-evoked myocardial apoptosis and sustains ventricular performance in rats through PAC1 activation, entailing PKA/Akt-Bad signaling enhancement and mitochondrial death pathway suppression. These data position PACAP as an attractive therapeutic option for CME-linked cardiac compromise.