Role and Mechanism of Notch1 in Cardiomyocyte Response to Mechanical Stretch in Hypertensive Cardiac Hypertrophy and NSAID Intervention

This study investigates the role and mechanisms of Notch1 in cardiomyocytes under mechanical stretch in the context of hypertensive cardiac hypertrophy and NSAID intervention. Using adult Sprague-Dawley rats, cardiomyocytes were isolated and cultured to establish a mechanical stretch model. Various intensities of mechanical stretch were applied to observe the expression and distribution of Notch1 and related signaling proteins (e. g., Hes1, KLF2, FABP4). Techniques such as Western blot, ELISA, immunofluorescence, electron microscopy, and RT-PCR were employed to comprehensively assess cardiomyocyte responses. Experimental groups included controls, mechanical stretch, siRNA, 50 μM DAPT, and Notch1 overexpression, with data collected at multiple time points. Results indicated that mechanical stretch significantly activated the Notch signaling pathway, promoting cardiomyocyte hypertrophy. In contrast, siRNA-mediated Notch1 silencing, DAPT inhibition of the Notch pathway, or NSAID treatment effectively suppressed stretch-induced hypertrophy. Notch1 plays a crucial role in cell-cell interactions, alignment, and proliferation, possibly regulating cardiomyocyte structure and function. NSAIDs, by modulating the Notch pathway, markedly inhibit cardiac hypertrophy, suggesting a novel therapeutic approach for hypertensive cardiac hypertrophy.