Tissue & cell · 2026
Pituitary adenylate cyclase-activating polypeptide attenuates coronary microembolization-induced myocardial apoptosis via PAC1 receptor activation in rats.
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Li Lingjuan, Zhang Aihui, Liang Suozhu, Zhang Haitao, Xu Hui, Shi Weiwei
Аннотация
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.
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.