GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306012/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306012GEOGSEfalseTemporal inhibition of ADAM17 in fibroblasts reduces stiffness and promotes vascularization following myocardial infarctionMyocardial infarction (MI) triggers a complex remodelling process that leads to heat failure if uncontrolled. A Disintegrin and metalloproteinase-17 (ADAM17), a transmembrane sheddase, is upregulated in patients with ischemic cardiomyopathy, colocalized to myofibroblasts (myoFB) in the infarct tissues. Fibroblasts are key players in post-MI scar formation and exist in different states with diverse functions. Using mice with inducible Adam17 deletion in homeostatic FBs (Adam17 FB-KD ), or activated FBs (Adam17 myoFB-KD ), we found that ADAM17 loss in homeostatic FBs impaired infarct formation post-MI and increased mortality due to left ventricular (LV) rupture. Conversely, ADAM17 loss in myoFBs limited infarct expansion, LV dilation and dysfunction up to 4 weeks post-MI. Ex vivo and in vitro experiments revealed that the beneficial effects in Adam17 myoFB-KD mice are due to reduced stiffness of the infarct tissue through suppressing activation of EGFR-YAP-pathway, which promoted vascularization and thereby limited infarct expansion. Pharmacological inhibition of ADAM17 prior to MI was ineffective, but short-term ADAM17 inhibition after MI by targeting myoFBs significantly alleviated the adverse LV remodeling and dysfunction with beneficial effects up to 4wks post-MI. Our study identifies a short-term therapeutic window for ADAM17 inhibition to prevent long-term adverse remodeling, dysfunction and heart failure post-MI.2026/07/22GSE306012GSM9191554GSM9191576GSM9191575GSM9191553GSM9191574GSM9191552GSM9191573GSM9191558GSM9191557GSM9191579GSM9191578GSM9191577GSM9191555GSM9191583GSM9191560GSM9191582GSM9191581GSM9191580GSM9191565GSM9191563GSM9191585GSM9191584GSM9191562GSM9191568GSM9191567GSM9191572GSM9191571GSM919157030172306012Mus musculus[41524432]