Effects and mechanism of pterostilbene on angiotensin II-induced myocardial hypertrophy and fibrosis

Pressure overload-induced cardiac hypertrophy and myocardial fibrosis constitute key pathological substrates of heart failure and arrhythmias. This study investigates the protective effects of pterostilbene, a natural small-molecule phenolic compound, against angiotensin II (Ang II)-induced myocardial hypertrophy and fibrosis, and elucidates the underlying mechanisms. Eighteen C57BL/6J mice are randomly allocated into control, Ang II model, and pterostilbene treatment groups. Echocardiographic assessment demonstrates that compared with controls, Ang II administration significantly increases the heart weight-to-body weight ratio and impairs cardiac function. Histopathological analysis reveals pronounced myocardial fibrosis in the model group, accompanied by elevated expression of Collagen I and Collagen III. Notably, pterostilbene treatment significantly attenuates cardiac hypertrophy, improves cardiac function, and ameliorates myocardial fibrosis. Mechanistically, Ang II stimulation markedly downregulates miR-138-5p expression, whereas oxidative stress-induced growth inhibitor 1 (OSGIN1) is identified as its direct target. Pterostilbene upregulates miR-138-5p and downregulates OSGIN1expression within myocardial tissue. Furthermore, serum hydroxyproline levels are significantly elevated in Ang II-treated mice but are reduced following pterostilbene administration. In vitro assays further confirm that pterostilbene alleviates Ang II-induced cardiomyocyte hypertrophy and fibrosis concomitant with increased miR-138-5p expression. Dual-luciferase reporter assays confirmed the direct binding between miR-138-5p and OSGIN1, and OSGIN1 knockdown further enhanced the anti-hypertrophic effects of pterostilbene. Collectively, these findings demonstrate that pterostilbene effectively ameliorates Ang II-induced myocardial hypertrophy and fibrosis, potentially via the upregulation of miR-138-5p, highlighting its therapeutic potential for heart failure and arrhythmias.