Extracts of the sprout of Polygonum sachalinensis suppress the p300-histone acetyltransferase activity and the development of heart failure after myocardial infarction in rats

Objectives: Extracts of the sprout of Polygonum sachalinensis (ESPS) have been reported to exert various bioactive effects; however, their effects on cardiomyocyte hypertrophy and heart failure have not been investigated. This study aimed to clarify whether ESPS suppresses cardiomyocyte hypertrophy and attenuates the development of heart failure after myocardial infarction (MI), and whether these effects involve inhibition of p300-histone acetyltransferase (HAT) activity. Methods: Primary cultured rat cardiomyocytes were treated with ESPS (100, 300, or 1000 µg/mL) and stimulated with phenylephrine. Hypertrophic responses, transcriptional activity of hypertrophy-related genes, and histone H3 lysine 9 (H3K9) acetylation were assessed. The inhibitory effect of ESPS on p300-HAT activity was examined using an in vitro HAT assay. For in vivo analysis, rats with moderate MI (left ventricular fractional shortening ≤ 40%, assessed by echocardiography) were randomized to receive vehicle or ESPS (0.3 or 1 g/kg per day) beginning 1 week after MI surgery, and cardiac function and remodeling were evaluated 8 weeks after MI. Results: ESPS inhibited PE-induced cardiomyocyte hypertrophy, suppressed hypertrophic gene transcription, and reduced histone H3K9 acetylation. ESPS inhibited p300-HAT activity in vitro (IC50 = 262 µg/mL). In MI rats, ESPS (1 g/kg) markedly suppressed the MI-induced reduction in fractional shortening and attenuated cardiomyocyte hypertrophy, interstitial fibrosis, hypertrophic gene expression, and histone H3K9 acetylation. Conclusion: ESPS alleviates the development of post-MI heart failure, as evidenced by improved left ventricular systolic function, attenuated cardiac hypertrophy and fibrosis, and at least in part by inhibition of p300-HAT–associated histone H3K9 acetylation.