Key result
Fibroblast-specific overexpression of miR-425-5p markedly inhibited cardiac fibroblast proliferation and differentiation, alleviating myocardial fibrosis, cardiac hypertrophy and systolic dysfunction.
Why the study?
Pathological activation of cardiac fibroblasts contributes to pressure overload-induced cardiac remodelling and heart failure, and miR-425 may be involved, but the specific role and mechanisms of fibroblast-derived miR-425-5p remained unclear.
Does fibroblast-specific overexpression of miR-425-5p alleviate cardiac remodelling in a mouse model of pressure overload-induced heart failure?
Does fibroblast-specific overexpression of miR-425-5p alleviate cardiac remodelling in a mouse model of pressure overload-induced heart failure?
Fibroblast-derived miR-425-5p mitigates pressure overload-induced heart failure in mice by inhibiting TGF-β1/Smad signalling, highlighting it as a potential therapeutic target.
Hypothesis-generating for miR-425-5p in cardiac fibrosis; leaves open translation to human HF therapy.
The pathological activation of cardiac fibroblasts (CFs) plays a crucial role in the development of pressure overload-induced cardiac remodelling and subsequent heart failure (HF). Growing evidence demonstrates that multiple microRNAs (miRNAs) are abnormally expressed in the pathophysiologic process of cardiovascular diseases, with miR-425 recently reported to be potentially involved in HF. In this study, we aimed to investigate the effects of fibroblast-derived miR-425-5p in pressure overload-induced HF and explore the underlying mechanisms. C57BL/6 mice were injected with a recombinant adeno-associated virus specifically designed to overexpress miR-425-5p in CFs, followed by transverse aortic constriction (TAC) surgery. Neonatal mouse CFs (NMCFs) were transfected with miR-425-5p mimics and subsequently stimulated with angiotensin II (Ang II). We found that miR-425-5p levels were significantly downregulated in HF mice and Ang II-treated NMCFs. Notably, fibroblast-specific overexpression of miR-425-5p markedly inhibited the proliferation and differentiation of CFs, thereby alleviating myocardial fibrosis, cardiac hypertrophy and systolic dysfunction. Mechanistically, the cardioprotective actions of miR-425-5p may be achieved by targeting the TGF-β1/Smad signalling. Interestingly, miR-425-5p mimics-treated CFs could also indirectly affect cardiomyocyte hypertrophy in this course. Together, our findings suggest that fibroblast-derived miR-425-5p mitigates TAC-induced HF, highlighting miR-425-5p as a potential diagnostic and therapeutic target for treating HF patients.
No takes yet. Share an insight, caveat, or question.
Zhou et al. (2024) studied Heart failure. Fibroblast-specific overexpression of miR-425-5p was evaluated on Myocardial fibrosis, cardiac hypertrophy and systolic dysfunction. Fibroblast-specific overexpression of miR-425-5p markedly inhibited cardiac fibroblast proliferation and differentiation, alleviating myocardial fibrosis, cardiac hypertrophy and systolic dysfunction.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: