{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T02:17:40Z","timestamp":1755224260495,"version":"3.43.0"},"reference-count":55,"publisher":"EDP Sciences","issue":"1-2","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":202,"URL":"https:\/\/www.edpsciences.org\/en\/authors\/copyright-and-licensing"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biologie Aujourd\u2019hui"],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:p>La physiopathologie de l\u2019insuffisance cardiaque (IC) apr\u00e8s infarctus du myocarde (IM) impliquerait, comme dans l\u2019hypertension art\u00e9rielle (HTA), une hyperactivit\u00e9 du syst\u00e8me r\u00e9nine-angiotensine (SRA) c\u00e9r\u00e9bral et une hyperactivit\u00e9 sympathique. Parmi les principaux peptides effecteurs du SRA c\u00e9r\u00e9bral, l\u2019angiotensine II (AngII) et l\u2019angiotensine III (AngIII) activent de fa\u00e7on similaire les r\u00e9cepteurs des angiotensines de type 1 (AT1), augmentant ainsi la pression art\u00e9rielle (PA) et induisant une dysfonction cardiaque apr\u00e8s IM. L\u2019AngII \u00e9tant convertie <jats:italic>in vivo<\/jats:italic> en AngIII, la nature du peptide effecteur restait \u00e0 pr\u00e9ciser. Nous avons identifi\u00e9 les enzymes impliqu\u00e9es dans le m\u00e9tabolisme des angiotensines c\u00e9r\u00e9brales et d\u00e9velopp\u00e9 des inhibiteurs sp\u00e9cifiques et s\u00e9lectifs. Ces \u00e9tudes ont r\u00e9v\u00e9l\u00e9 le r\u00f4le cl\u00e9 de l\u2019AngIII dans le contr\u00f4le de la PA et de la fonction cardiaque, mettant en \u00e9vidence l\u2019aminopeptidase A (APA) c\u00e9r\u00e9brale, l\u2019enzyme responsable de la formation de l\u2019AngIII c\u00e9r\u00e9brale, comme cible th\u00e9rapeutique potentielle pour traiter l\u2019HTA et l\u2019IC post-IM. Cela a conduit au d\u00e9veloppement des inhibiteurs de l\u2019APA \u00e0 action centrale, actifs par voie orale, le firibastat et le QGC606, test\u00e9s dans diff\u00e9rents mod\u00e8les exp\u00e9rimentaux murins d\u2019HTA et d\u2019IC jusqu\u2019\u00e0 l\u2019essai clinique de phase 2 chez le patient apr\u00e8s IM.<\/jats:p>","DOI":"10.1051\/jbio\/2025004","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T07:49:51Z","timestamp":1753170591000},"page":"25-36","source":"Crossref","is-referenced-by-count":0,"title":["Inhibiteurs de l\u2019aminopeptidase A \u00e0 action centrale, actifs par voie orale, dans l\u2019insuffisance cardiaque apr\u00e8s infarctus du myocarde\u00a0: du d\u00e9veloppement jusqu\u2019\u00e0 l\u2019essai clinique de Phase II"],"prefix":"10.1051","volume":"219","author":[{"given":"Sol\u00e8ne 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