Key result
BRCA2 overexpression attenuates angiotensin II-induced cardiac hypertrophy and fibrosis in preclinical models.
Why the study?
Loss of BRCA2 exacerbates cardiomyocyte apoptosis and heart failure progression, raising the question of whether its upregulation could alleviate hypertrophic cardiomyopathy.
Does BRCA2 overexpression improve cardiac hypertrophy, fibrosis, inflammation, and apoptosis in Angiotensin II-treated mice?
Does BRCA2 overexpression improve cardiac hypertrophy, fibrosis, inflammation, and apoptosis in Angiotensin II-treated mice?
BRCA2 overexpression mitigates pathological cardiac hypertrophy, fibrosis, inflammation, and apoptosis in preclinical models, suggesting it as a potential therapeutic target for hypertrophic cardiomyopathy.
Loss of breast cancer susceptibility gene 2 (BRCA2) function was found to exacerbate doxorubicin-mediated cardiomyocyte apoptosis and promote heart failure progression. We hypothesized that upregulation of BRCA2 may alleviate hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy was established in mice via chronic angiotensin II (Ang II) administration (1.44 mg/kg/day) using osmotic minipumps. Cardiac BRCA2 expression was significantly downregulated in Ang II-treated mice. Cardiac hypertrophy triggered by Ang II in mice was significantly attenuated upon BRCA2 overexpression. Similarly, in cultured primary cardiomyocytes, Ang II-induced hypertrophic responses were suppressed by BRCA2 upregulation. The cardiac fibrosis was significantly attenuated after upregulation of BRCA2 in Ang II-induced hypertrophic cardiomyopathy. The myocardial inflammatory response to Ang II, characterized by elevated interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) levels, was markedly reduced with BRCA2 overexpression. The apoptotic biomarkers including Bax and cleaved caspase 3 (CC3) increased in the heart of hypertrophic cardiomyopathy, and attenuated after upregulation of BRCA2. These results indicated that upregulation of BRCA2 could improve hypertrophic cardiomyopathy. BRCA2 alleviated cardiac hypertrophy via attenuation of inflammation and apoptosis.
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Liu et al. (2026) studied Hypertrophic cardiomyopathy. BRCA2 overexpression (via LV-BRCA2) vs. LV-GFP was evaluated on Cardiac hypertrophy (assessed by HW, HW/BW, HW/TL, and echocardiography parameters) (p=<0.05). BRCA2 overexpression significantly attenuated angiotensin II-induced hypertrophic cardiomyopathy and cardiac fibrosis in mice by inhibiting inflammatory signaling and apoptosis.
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