Connexin 43 deficiency is associated with reduced myocardial scar size and attenuated tgfβ1 signaling after transient coronary occlusion in conditional knock-out mice
Valls-Lacalle, Laura (Universitat Autònoma de Barcelona. Departament de Medicina)
Consegal, Marta (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ruiz Meana, Marisol (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Benito, Begoña (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Inserte, Javier (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Barba, Ignasi (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ferreira-Gonzalez, Ignacio (Universitat Autònoma de Barcelona. Departament de Medicina)
Rodríguez-Sinovas, Antonio (Universitat Autònoma de Barcelona. Departament de Medicina)

Date:	2020
Abstract:	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.
Note:	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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Connexin 43 ; Left ventricular remodeling ; Collagen ; Ischemia-reperfusion ; Myocardial infarct
Published in:	Biomolecules, Vol. 10 Núm. 4 (april 2020) , p. 651, ISSN 2218-273X

DOI: 10.3390/biom10040651
PMID: 32340244

10 p, 2.0 MB

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