Curcumin protects against pressure overload-induced heart failure via epigenetic modulation of the Sfrp1/Wnt/β-catenin pathway

Abstract

Objective: To explore whether curcumin alleviates transverse aortic constriction (TAC)-induced heart failure by modulating the DNMT-Sfrp1-Wnt/β-catenin signaling. Methods: Male C57BL/6J mice underwent TAC or sham surgery and then received vehicle or curcumin at 50, 100, or 200 mg/kg/day for 4 weeks. Cardiac structure and performance were evaluated by echocardiography together with invasive hemodynamics, while apoptosis, DNMT activity, Sfrp1 promoter methylation, and Wnt/β-catenin signaling were examined using TUNEL staining, bisulfite sequencing, quantitative RT-PCR, and Western blotting. Results: Compared with untreated TAC mice, curcumin preserved left ventricular systolic function, lowered NT-proBNP, and mitigated ventricular enlargement. It also reduced cardiomyocyte apoptosis, decreased Bax and cleaved caspase-3, and increased Bcl-2. Furthermore, curcumin downregulated Dnmt1, Dnmt3a, and Dnmt3b, reduced total DNMT activity, alleviated methylation of the Sfrp1 promoter, restored Sfrp1 expression, and diminished nuclear β-catenin as well as c-Myc and cyclin D1. Conclusions: Curcumin mitigates TAC-induced cardiac dysfunction and adverse remodeling by modulating the DNMT-Sfrp1-Wnt/β-catenin pathway. These data indicate that curcumin may act as an epigenetic regulator in pathological cardiac remodeling.

Keywords

Curcumin / DNA methyltransferase / Sfrp1 / Wnt/β-catenin signaling / Transverse aortic constriction / Heart failure

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