Viczenczova Csilla, Kura Branislav, Chaudagar Kiranj K, Szeiffova Bacova Barbara, Egan Benova Tamara, Barancik Miroslav, Knezl Vladimir, Ravingerova Tana, Tribulova Narcis, Slezak Jan
a Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
b L.M. College of Pharmacy, Ahmedabad, India.
Can J Physiol Pharmacol. 2017 Aug;95(8):911-919. doi: 10.1139/cjpp-2016-0680. Epub 2017 Apr 29.
We aimed to explore whether myocardial intercellular channel protein connexin-43 (Cx43) along with PKCε and MMP-2 might be implicated in responses to acute cardiac injury induced by 2 distinct sublethal interventions in Wistar rats. Animals underwent either single chest irradiation at dose of 25 Gy or subcutaneous injection of isoproterenol (ISO, 120 mg/kg) and were compared with untreated controls. Forty-two days post-interventions, the hearts were excised and left ventricles were used for analysis. The findings showed an increase of total as well as phosphorylated forms of myocardial Cx43 regardless of the type of interventions. Enhanced phosphorylation of Cx43 coincided with increased PKCε expression in both models. Elevation of Cx43 was associated with its enhanced distribution on lateral surfaces of the cardiomyocytes in response to both interventions, while focal areas of fibrosis without Cx43 were found in post-ISO but not post-irradiated rat hearts. In parallel, MMP-2 activity was decreased in the former while increased in the latter. Cardiac function was maintained and the susceptibility of the hearts to ischemia or malignant arrhythmias was not deteriorated 42 days after interventions when compared with controls. Altogether, the findings indicate that myocardial Cx43 is most likely implicated in potentially salutary responses to acute heart injury.
我们旨在探究心肌细胞间通道蛋白连接蛋白43(Cx43)以及蛋白激酶Cε(PKCε)和基质金属蛋白酶-2(MMP-2)是否参与了Wistar大鼠由两种不同的亚致死性干预诱导的急性心脏损伤反应。动物接受25 Gy剂量的单次胸部照射或皮下注射异丙肾上腺素(ISO,120 mg/kg),并与未处理的对照组进行比较。干预后42天,取出心脏,使用左心室进行分析。结果显示,无论干预类型如何,心肌Cx43的总量以及磷酸化形式均增加。在两个模型中,Cx43磷酸化增强与PKCε表达增加同时出现。两种干预均使Cx43升高,并使其在心肌细胞侧面的分布增强,而在ISO处理后的大鼠心脏中发现了无Cx43的局灶性纤维化区域,而照射后大鼠心脏中未发现。同时,前者的MMP-2活性降低,而后者升高。与对照组相比,干预后42天心脏功能得以维持,心脏对缺血或恶性心律失常的易感性未恶化。总之,这些结果表明心肌Cx43很可能参与了对急性心脏损伤的潜在有益反应。