{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306012/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306012"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Temporal inhibition of ADAM17 in fibroblasts reduces stiffness and promotes vascularization following myocardial infarction","description":"Myocardial 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.","dates":{"publication":"2026/07/22"},"accession":"GSE306012","cross_references":{"GSM":["GSM9191554","GSM9191576","GSM9191575","GSM9191553","GSM9191574","GSM9191552","GSM9191573","GSM9191558","GSM9191557","GSM9191579","GSM9191578","GSM9191577","GSM9191555","GSM9191583","GSM9191560","GSM9191582","GSM9191581","GSM9191580","GSM9191565","GSM9191563","GSM9191585","GSM9191584","GSM9191562","GSM9191568","GSM9191567","GSM9191572","GSM9191571","GSM9191570"],"GPL":["30172"],"GSE":["306012"],"taxon":["Mus musculus"],"PMID":["[41524432]"]}}