Lower expression of BRCA1 in cardiomyoblast alters the expression of apoptotic, inflammatory and metabolic pathway genes, and enhances catecholamine-induced hypertrophic response.

BRCA1 (Breast Cancer Type 1) protein is well known for its critical role in DNA damage repair, genome stability, and tumor suppression. Recent studies suggest that BRCA1 also plays a broader role in the heart, maintaining genomic stability in cardiomyocytes and protecting them from stress-induced damage, although its exact function in cardiac cells remains unclear. Thus, we have explored its genotypic and phenotypic effects in BRCA1-knockdown H9c2 cells. Successful knockdown of BRCA1 was achieved by developing lentiviral particles containing BRCA1 shRNA. We found that knocking-down BRCA1 altered apoptotic genes, and downregulated inflammatory and metabolic genes. It also upregulated hypertrophic genes in H9c2 cells, which is consistent with reports linking BRCA1 deficiency to increased susceptibility to apoptosis and maladaptive cardiac remodeling. Moreover, isoproterenol-induced hypertrophy in these cells demonstrated further genetic alterations in the expression of hypertrophic and fibrotic genes, indicating an enhanced stress response in the absence of BRCA1. Therefore, physiological levels of BRCA1 expression are essential to maintain normal homeostasis of cardiac cells, and its depletion may result in remodeling of the heart, especially in the presence of stressful stimuli.