Affiliation:
1. Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang 330008, China
2. Department of Cardiology, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Affiliated Hospital of Sun Yat-sen University, Nanchang 330008, China
Abstract
Cardiomyocyte apoptosis, neural remodeling, and gap junction channel change play critical roles in ventricular arrhythmia (VA) after acute myocardial infarction (AMI). Urolithin B (UB), one of the gut metabolites of ellagitannins, a class of antioxidant polyphenols, has various biological activities, but its direct role in cardiomyocyte apoptosis, neural remodeling, and gap junction channel change after AMI remains elusive. We investigated whether urolithin B reduced susceptibility of myocardial arrhythmic after myocardial infarction (MI). In vitro, the cardiomyocytes were subjected to hypoxia (94% N2/5% CO2/1% O2) for 3 hours. Cardiomyocyte apoptosis was assessed by TUNEL staining and western blotting. Urolithin B was found to decrease the number of apoptotic cells after hypoxia. Moreover, there was a substantial decrease in the expression of neural remodeling markers in the urolithin B treatment group. Urolithin B significantly increased the expression level of gap junction channel protein. Mechanistically, urolithin B inhibited cardiomyocyte apoptosis by activating Akt/the mammalian target of rapamycin (mTOR) pathway, and the protection of urolithin B against cardiomyocyte apoptosis was compromised with Akt gene silencing. Furthermore, urolithin B suppressed nuclear translocation of nuclear factor-kB (NF-κB) to facilitate nerve remodeling. Taken together, our findings suggested that UB reduced the occurrence of myocardial arrhythmias after hypoxia via regulation of the Akt/mTOR pathway and NF-κB nuclear translocation, which highlights the potential of UB as a novel therapy for ischemic heart disease.
Subject
Biochemistry (medical),Clinical Biochemistry,Genetics,Molecular Biology,General Medicine
Cited by
8 articles.
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