biostudies-literatureZhang LNational Natural Science Foundation of ChinaNatural Science Foundation of Fujian Province,China29https://www.ebi.ac.uk/biostudies/studies/S-EPMC12857088biostudies-literatureUnknown25(1)<h4>Background</h4>In recent years, except for the well-known heart failure with reduced ejection fraction (HFrEF), the incidence of heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) among the classification of heart failure (HF) has been increasing. However, due to their complex mechanisms, current research remains insufficient to address clinical needs.<h4>Methods and results</h4>Utilizing wild-type (WT), miR-30a-5p knockout (KO), and overexpression (OE) murine models combined with estrogen modulation and ovariectomy (OVX), this study delineates sex-specific regulatory networks in HF pathogenesis. Female KO mice lost the inherent resistance of WT females to HFpEF induction via 24-week HFD/L-NAME, whereas males exhibiteCardiovascular diabetologySex-specific cardioprotective role of miR-30a-5p through estrogen-dependent mechanisms in a mouse model of heart failure.PMC12857088822003732024J0114232025J0114892023J011677Li GYu LQChen JFWang RFu GQuan MZhang XCZhang LZhang SYfalseSex-specific cardioprotective role of miR-30a-5p through estrogen-dependent mechanisms in a mouse model of heart failure.<h4>Background</h4>In recent years, except for the well-known heart failure with reduced ejection fraction (HFrEF), the incidence of heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) among the classification of heart failure (HF) has been increasing. However, due to their complex mechanisms, current research remains insufficient to address clinical needs.<h4>Methods and results</h4>Utilizing wild-type (WT), miR-30a-5p knockout (KO), and overexpression (OE) murine models combined with estrogen modulation and ovariectomy (OVX), this study delineates sex-specific regulatory networks in HF pathogenesis. Female KO mice lost the inherent resistance of WT females to HFpEF induction via 24-week HFD/L-NAME, whereas males exhibite2026-01-01T00:00:00Z2026 Jan2026-06-13T05:30:29.158Z2026-06-13T03:09:14.598ZS-EPMC128570884161238910.1186/s12933-026-03090-7