Arai Takahide, Kanazawa Hideaki, Kimura Kensuke, Munakata Masahito, Yamakawa Hiroyuki, Shinmura Ken, Yuasa Shinsuke, Sano Motoaki, Fukuda Keiichi
Division of Cardiology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
International Medical Center, Department of Cardiology, Saitama Medical University, Saitama, Japan.
Front Neurosci. 2022 Nov 3;16:1013712. doi: 10.3389/fnins.2022.1013712. eCollection 2022.
Substantial emotional or physical stress may lead to an imbalance in the brain, resulting in stress cardiomyopathy (SC) and transient left ventricular (LV) apical ballooning. Even though these conditions are severe, their precise underlying mechanisms remain unclear. Appropriate animal models are needed to elucidate the precise mechanisms. In this study, we established a new animal model of epilepsy-induced SC. The SC model showed an increased expression of the acute phase reaction protein, c-Fos, in the paraventricular hypothalamic nucleus (PVN), which is the sympathetic nerve center of the brain. Furthermore, we observed a significant upregulation of neuropeptide Y (NPY) expression in the left stellate ganglion (SG) and cardiac sympathetic nerves. NPY showed neither positive nor negative inotropic and chronotropic effects. On the contrary, NPY could interrupt β-adrenergic signaling in cardiomyocytes when exposure to NPY precedes exposure to noradrenaline. Moreover, its elimination in the left SG siRNA treatment tended to reduce the incidence of SC. Thus, our results indicated that upstream sympathetic activation induced significant upregulation of NPY in the left SG and cardiac sympathetic nerves, resulting in cardiac dysfunctions like SC.
严重的情绪或身体应激可能导致大脑失衡，引发应激性心肌病（SC）和短暂性左心室心尖气球样变。尽管这些病症很严重，但其确切的潜在机制仍不清楚。需要合适的动物模型来阐明确切机制。在本研究中，我们建立了一种新的癫痫诱发SC动物模型。在作为大脑交感神经中枢的室旁下丘脑核（PVN）中，SC模型显示急性期反应蛋白c-Fos的表达增加。此外，我们观察到左星状神经节（SG）和心脏交感神经中神经肽Y（NPY）表达显著上调。NPY既无正性也无负性变力和变时作用。相反，当在去甲肾上腺素暴露之前先暴露于NPY时，NPY可中断心肌细胞中的β-肾上腺素能信号传导。此外，通过小干扰RNA（siRNA）处理消除左SG中的NPY倾向于降低SC的发生率。因此，我们的结果表明上游交感神经激活导致左SG和心脏交感神经中NPY显著上调，从而导致如SC的心脏功能障碍。
