4-Hydroxybenzaldehyde Attenuates Iso proterenol-induced Cardiac Fibrosis via TGF-β-Smad2/3 Signaling Pathway

This study aims to investigate the cardioprotective effects of 4-Hydroxybenzaldehyde (4-HBA) against isoproterenol (ISO)-induced cardiac fibrosis and to elucidate the underlying mechanisms. In vivo, cardiac fibrosis was induced in C57BL/6 mice by subcutaneous injection of ISO, and the mice were treated with 4-HBA or a TGF-β inhibitor. Assessments using echocardiography, histopathology, and Western blotting demonstrated that 4-HBA significantly alleviated ISO-induced cardiac dysfunction, reduced collagen deposition, and attenuated apoptosis in mice. Mechanistically, 4-HBA inhibited TGF-β expression and Smad2/3 phosphorylation. In vitro, ISO was applied to cardiomyocytes (HL-1) and cardiac fibroblasts (MCFs), with or without 4-HBA or TGF-β inhibitor intervention. The results showed that 4-HBA suppressed HL-1 apoptosis and fibroblast proliferation, and significantly reduced the expression of extracellular matrix genes, TGF-β levels, and Smad2/3 phosphorylation in MCFs. These findings indicate that 4-HBA reduces myocardial injury while targeting the TGF-β/Smad2/3 pathway to attenuate cardiac fibrosis, highlighting its potential as a therapeutic agent for fibrotic cardiomyopathy.