Cardiovascular Diseases Research Group, Department of Cardiology, Vall d'Hebron University Hospital and Research Institute, Departament de Medicina, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain.
Biomolecules. 2020 Apr 23;10(4):651. 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.
先前的研究表明，杂合型 Cx43 小鼠在永久性冠状动脉阻塞后心肌瘢痕面积减小。然而，患有 ST 段抬高型心肌梗死的患者通常会进行快速冠状动脉血运重建，从而迅速恢复冠状动脉血流。因此，我们旨在评估使用 Cx43（对照组）和 Cx43 诱导型敲除（Cx43 含量：50%）小鼠进行短暂心肌缺血（45 分钟）后，再进行 14 天再灌注后，瘢痕大小和左心室重构的变化，并用载体或 4-羟基他莫昔芬（4-OHT）处理 Cx43 诱导型敲除（Cre-ER(T)-介导的 Cx43 floxed 等位基因的全局缺失）。短暂性冠状动脉闭塞后 14 天测量的瘢痕面积（苦味酸天狼星红）在载体和 4-OHT 处理的 Cx43 小鼠中与 Cx43 动物相似减少，具有正常的 Cx43 水平（15.78%±3.42%和 16.54%±2.31%与 25.40%±3.14%和 22.43%±3.88%在载体和 4-OHT 处理的小鼠中， = 0.027）。左心室扩张在两种 Cx43 缺陷型小鼠中均明显减轻（左心室舒张末期直径， = 0.037）。这些保护作用与再灌注后促转化生长因子β1（TGFβ1）表达增强减弱相关。总之，我们的数据表明，Cx43 缺乏在小鼠短暂性冠状动脉闭塞后诱导瘢痕形成的保护作用，这种作用与左心室重构减少和促 TGFβ1 表达减弱相关。
