Connecting sex differences, estrogen signaling, and microRNAs in cardiac fibrosis

摘要: Sex differences are evident in the pathophysiology of heart failure (HF). Progression HF is promoted by cardiac fibrosis and no fibrosis-specific therapies currently available. The fibrotic response mediated fibroblasts (CFs), a central event their phenotypic transition to pro-fibrotic myofibroblasts. These myofibroblasts may arise from various cellular origins including resident CFs epicardial endothelial cells. Both female subjects clinical studies animals experimental generally present less compared with males. This difference at least partially considered attributable ovarian hormone 17β-estradiol (E2). E2 signals via estrogen receptors regulate genes involved myofibroblast transition. Besides protein-coding genes, also regulates transcription microRNA that modulate fibrosis. dimorphism, E2, miRNAs form multi-level regulatory networks fibrosis, mechanism these not yet fully deciphered. Therefore, this review aimed summarizing current knowledge on sex differences, emphasizing microRNAs origins. KEY MESSAGES: • ERs fibroblast function. distinctly affect male pathophysiology. Sex, Sex-dimorphic E2-regulated mesenchymal