2026-04-17T05:51:23Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4563472026-03-13T07:38:58Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Valls-Lacalle, Laura author Consegal, Marta author Ruiz Meana, Marisol author Benito Villabriga, Begoña author Inserte, Javier author Barba, Ignasi author Ferreira-Gonzalez, Ignacio author Rodríguez Sinovas, Antonio author 2020 Funding: This research was funded by Fundació La Marató de TV3 (n◦. 201536-10) and the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (CIBERCV), cofinanced by the European Regional Development Fund (ERDF-FEDER, a way to build Europe). Antonio Rodríguez-Sinovas has a consolidated Miguel Servet contract. Previous studies demonstrated a reduction in myocardial scar size in heterozygous Cx43-mice subjected to permanent coronary occlusion. However, patients presenting with ST segment elevation myocardial infarction often undergo rapid coronary revascularization leading to prompt restoration of coronary flow. Therefore, we aimed to assess changes in scar size and left ventricular remodeling following transient myocardial ischemia (45 min) followed by 14 days of reperfusion using Cx43 (controls) and Cx43 inducible knock-out (Cx43 content: 50%) mice treated with vehicle or 4-hydroxytamoxifen (4-OHT) to induce a Cre-ER(T)-mediated global deletion of the Cx43 floxed allele. The scar area (picrosirius red), measured 14 days after transient coronary occlusion, was similarly reduced in both vehicle and 4-OHT-treated Cx43 mice, compared to Cx43 animals, having normal Cx43 levels (15.78% ± 3.42% and 16.54% ± 2.31% vs. 25.40% ± 3.14% and 22.43% ± 3.88% in vehicle and 4-OHT-treated mice, respectively, p = 0.027). Left ventricular dilatation was significantly attenuated in both Cx43-deficient groups (p = 0.037 for left ventricular end-diastolic diameter). These protective effects were correlated with an attenuated enhancement in pro-transforming growth factor beta 1 (TGFβ1) expression after reperfusion. In conclusion, our data demonstrate that Cx43 deficiency induces a protective effect on scar formation after transient coronary occlusion in mice, an effect associated with reduced left ventricular remodeling and attenuated enhancement in pro-TGFβ1 expression. Connexin 43 Left ventricular remodeling Collagen Ischemia-reperfusion Myocardial infarct Connexin 43 deficiency is associated with reduced myocardial scar size and attenuated tgfβ1 signaling after transient coronary occlusion in conditional knock-out mice