Tanscriptomic analysis examined the specific mechanisms by which Foxm1 defects in cardiac fibroblasts prevent cardiac remodeling induced by pressure overload
Cardiac fibroblasts (CFs) play a crucial role in cardiac remodeling, which is a common cause of heart failure (HF). However, the molecular mechanisms underlying the transformation of fibroblasts into myofibroblasts remain largely unknown. Foxm1 is well-known in various cardiovascular diseases. However, the role of Foxm1-driven CF activation in the progression of cardiac remodeling towards HF is still being investigated. In this study, we observed an upregulation of Foxm1 expression in samples obtained from patients with heart failure (HF) and in mice with transverse aortic constriction (TAC)-induced cardiac remodeling. Additionally, we discovered that inhibition of Foxm1 using the drug FDI-6 improved TAC-induced cardiac remodeling and attenuated the activation of cardiac fibroblasts (CFs). Furthermore, through our investigations, we found that Foxm1 was activated in Tcf21-Cre and PostnMCM transgenic mice subjected to TAC surgery, resulting in the activation of CFs and exerting an influence on the cardiac remodeling process. Overall design: To comprehensively explore the potential mechanisms underlying Foxm1-mediated cardiac remodeling, we conducted transcriptomic analyses in neonatal ventricular cardiac fibroblasts  (NVCFs) with Foxm1 knockdown or overexpression. RNA samples were collected from NVCFs in different experimental groups, including si-NC (negative control), si-Foxm1 (Foxm1 knockdown), Ang-II (angiotensin II stimulation), si-Foxm1+Ang-II (combined Foxm1 knockdown and angiotensin II stimulation), OE-NC (overexpression negative control), and OE-Foxm1 (Foxm1 overexpression).