Effects and associated mechanisms of cinnamic acid on early cardiac hypertrophy and fatty acid transport
Objective:To determine whether cinnamic acid(CA)plays a role in the pathological cardiac hypertrophy induced by transverse aortic constriction(TAC)and phenylephrine(PE),and based on the bioinformatics analysis,the corresponding mechanism were explored.Methods:TAC surgery was used to generate cardiac hypertrophy model in vivo.Cardiac hypertrophy was determined by heart mass index,wheat germ agglutinin(WGA)staining,and expression levels of cardiac hypertrophy markers,atrial natriuretic peptide(ANP).HE and Masson's Trichrome staining procedures were used to evaluate histopathologic changes.In vitro experiments were as follows:PE was adopted to induce cardiomyocyte hypertrophy in neonatal rat cardiomyocytes(NRCMs)in order to determine if CA was able to directly suppress cardiomyocyte hypertrophy.To detect hypertrophy induction,NRCMs were stained with rhodamine phalloidin and ANP.Differential gene expression was analyzed using RNA-seq data.Fatty acid transport was performed in NRCMs with BODIPYTM 500/510 probe.Real-time quantitative PCR(qPCR)and Western Blot(WB)were used to validate differential gene expression.Results:The in vivo findings:CA significantly antagonized TAC-induced left ventricular remodeling(P＜0.05).In vitro findings:CA significantly suppressed PE-induced cardiomyocyte hypertrophy(P＜0.05).RNA-seq analyses revealed that the expression of fatty acid transport-related genes was downregulated in PE-induced cardiomyocyte hypertrophy.And then BODIPYTM 500/510 staining demonstrated that CA significantly increased fatty acid transport in PE-induced cardiomyocyte hypertrophy(P＜0.05).The results of qPCR and WB showed that CA significantly inhibited the decrease of CPT1A expression in PE-stimulated NRCMs(P＜0.05).Conclusion:CA is effective at mitigating TAC-induced left ventricular remodeling in part by antagonizing the hypertrophic responses and promoting fatty acid transport through up-regulation of CPT1A in the PE-stimulated cardiomyocytes.
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