Boron Regulates Cardiac Fibrosis Via Modulating the Profibrotic and Apoptotic Pathway

Background: Cardiac fibrosis, involving excessive extracellular matrix and myofibroblast buildup, is crucial in remodeling of the failing heart. After myocardial damage, inflammatory and neurohormonal responses cause fibrotic scarring, but balanced inflammation is key to healing. Boron, a dietary trace mineral, aids extracellular matrix turnover, immune response and tissue repair, though its role in cardiac repair is unexplored. We investigated whether boron could regulate cardiac fibrosis by modulating the fibrotic and apoptotic pathways, potentially reducing fibrosis after myocardial infarction (MI). Methods: Sprague Dawley rats underwent MI via permanent ligation of the left anterior descending artery for 21 days to induce fibrosis and heart failure. Borax (a sodium salt of boron) was administered 7 days post-injury (4 mg/kg). Cardiac function was assessed by transthoracic echocardiography, while fibrosis, apoptosis, and mitochondrial integrity were evaluated using qRT-PCR, western blotting, immunohistochemistry, and confocal microscopy. Moreover, boron's effects on the mitochondrial membrane potential and Cyt c sequestration were examined in cardiac fibroblasts. Results: Boron treatment improved systolic and diastolic functions of the heart and reduced the BNP level (a marker of heart failure). Moreover, it showed a marked reduction in myocardial fibrosis evidenced by the decreased expression of fibrotic markers: α-SMA, Collagen 1a, CTGF, and Fibronectin in the post-MI rat hearts compared to that of saline controls. It also reduced cardiomyocyte apoptosis confirmed by reduced TUNEL positive cells in left ventricular sections of the hearts and enhanced mitochondrial membrane integrity evidenced by sequestration of Cyt c in confocal microscopy. Conclusion: Boron supplementation following MI-induced cardiac fibrosis improved cardiac systolic and diastolic function, reduced fibrosis, and enhanced mitochondrial integrity in rats. It may exert anti-fibrotic effects through mitigating the pro-fibrotic and fibroblast activation pathways and modulating the extracellular matrix turnover mechanisms, suggesting a new approach to prevent heart remodeling after injury. Restoring the balance between the anti- and pro-fibrotic signaling with boron could offer valuable insights into cardiac fibrosis and remodeling. National Institutes of Health (NIH) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.