Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Int J Mol Sci. 2022 Oct 9;23(19):11978. doi: 10.3390/ijms231911978.
Contraction band necrosis (CBN) is a common abnormality found in the myocardium of cocaine abusers, but is rarely reported in experimental models of cocaine abuse. Connexin 43 (Cx43) is essential for cardiac intercellular communication and the propagation of CBN. Under stress or injury, cardiac Cx43 is dephosphorylated, which is related to cardiomyocyte dysfunction and pathogenesis, whereas adiponectin exerts beneficial effects in the myocardium. In this study, we explore the effects of cocaine on cardiac Cx43 in vivo. Rats were administered cocaine via the tail vein at 20 mg/kg/day for 14 days, and showed widespread CBN, microfocal myocarditis and myocardial fibrosis, corresponding to a dysfunction of cardiac mitochondria under increased oxidative stress. The increase in dephosphorylated cardiac Cx43 and its negative correlation with the myocardial distribution of CBN after cocaine administration were determined. In addition, apoptosis and necroptosis, as well as increased adiponectin levels, were observed in the myocardium after cocaine exposure. Accordingly, we found altered profiles of cardiac Cx43, CBN and its negative correlation with dephosphorylated cardiac Cx43, and the possible involvement of adiponectin in the myocardium after 14 days of cocaine administration. The latter might play a protective role in the cardiotoxicity of cocaine. The current findings would be beneficial for establishing novel therapeutic strategies in cocaine-induced cardiac consequences.
收缩带坏死(CBN)是可卡因滥用者心肌中常见的异常,但在可卡因滥用的实验模型中很少报道。连接蛋白 43(Cx43)对心脏细胞间通讯和 CBN 的传播至关重要。在应激或损伤下,心脏 Cx43 去磷酸化,与心肌细胞功能障碍和发病机制有关,而脂联素在心肌中发挥有益作用。在这项研究中,我们探讨了可卡因对体内心脏 Cx43 的影响。大鼠尾静脉给予可卡因 20mg/kg/天,共 14 天,表现出广泛的 CBN、微灶性心肌炎和心肌纤维化,对应于氧化应激增加时心脏线粒体功能障碍。确定了可卡因给药后去磷酸化心脏 Cx43 的增加及其与 CBN 在心肌中分布的负相关。此外,在可卡因暴露后心肌中观察到细胞凋亡和坏死性凋亡以及脂联素水平升高。因此,我们发现了心脏 Cx43 的改变谱、CBN 及其与去磷酸化心脏 Cx43 的负相关,以及脂联素在可卡因给药 14 天后可能参与心肌。后者可能在可卡因的心脏毒性中发挥保护作用。目前的研究结果将有助于为可卡因引起的心脏后果建立新的治疗策略。