Connexin 43 Deficiency Is Associated with Reduced Myocardial Scar Size and Attenuated TGFβ1 Signaling after Transient Coronary Occlusion in Conditional Knock-Out Mice

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2020-04, Vol.10 (4), p.651
• Main Authors: Valls-Lacalle, Laura, Consegal, Marta, Ruiz-Meana, Marisol, Benito, Begoña, Inserte, Javier, Barba, Ignasi, Ferreira-González, Ignacio, Rodríguez-Sinovas, Antonio
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers - metabolism; Cardiomyocytes; Cicatrix - pathology; collagen; Connective Tissue Growth Factor - metabolism; Connexin 43; Connexin 43 - deficiency; Connexin 43 - metabolism; Coronary Occlusion - diagnostic imaging; Coronary Occlusion - metabolism; Coronary Occlusion - pathology; Coronary Occlusion - physiopathology; Growth factors; Heart; Heart attacks; Ischemia; ischemia–reperfusion; Laboratory animals; left ventricular remodeling; Male; Mice, Inbred C57BL; Mice, Knockout; myocardial infarct; Myocardial infarction; Myocardial ischemia; Myocardium - pathology; NF-kappa B - metabolism; Occlusion; Ostomy; Phosphorylation; Reperfusion; Signal Transduction; Smad Proteins - metabolism; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; Variance analysis; Ventricle; Ventricular Remodeling
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom10040651

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, = 0.027). Left ventricular dilatation was significantly attenuated in both Cx43-deficient groups ( = 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.