Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure and sudden death. The hallmark pathological findings are progressive myocyte loss and fibro fatty replacement, with a predilection for the right ventricle. This study focuses on the adipose tissue formation in cardiomyocyte by considering the signal transduction pathways including Wnt/[inline-formula removed]-catenin and Wnt/Ca2+ regulation system. These pathways are modelled and analysed using stochastic petri nets (SPN) in order to increase our comprehension of ARVC and in turn its treatment regimen. The Wnt/[inline-formula removed]-catenin model predicts that the dysregulation or absence of Wnt signalling, inhibition of dishevelled and elevation of glycogen synthase kinase 3 along with casein kinase I are key cytotoxic events resulting in apoptosis. Moreover, the Wnt/Ca2+ SPN model demonstrates that the Bcl2 gene inhibited by c-Jun N-terminal kinase protein in the event of endoplasmic reticulum stress due to action potential and increased amount of intracellular Ca2+ which recovers the Ca2+ homeostasis by phospholipase C, this event positively regulates the Bcl2 to suppress the mitochondrial apoptosis which causes ARVC.

中文翻译：

---

用于分析致心律失常性右心室心肌病中 Wnt/[去除内联公式]-连环蛋白和 Wnt/Ca2+ 信号通路行为的 Petri 网建模方法。

致心律失常性右心室心肌病 (ARVC) 是一种遗传性心肌疾病，可导致心律失常、心力衰竭和猝死。标志性的病理发现是进行性肌细胞丢失和纤维脂肪替代，右心室好发。本研究通过考虑包括 Wnt/[inline-formula removed]-catenin 和 Wnt/Ca2+ 调节系统在内的信号转导途径，重点关注心肌细胞中脂肪组织的形成。使用随机 petri 网 (SPN) 对这些途径进行建模和分析，以增加我们对 ARVC 的理解，进而增加其治疗方案。Wnt/[删除内联公式]-连环蛋白模型预测 Wnt 信号失调或缺失，抑制糖原合酶激酶 3 和酪蛋白激酶 I 的蓬乱和升高是导致细胞凋亡的关键细胞毒性事件。此外，Wnt/Ca2+ SPN 模型表明，在发生内质网应激时，由于动作电位和细胞内 Ca2+ 量增加，C-Jun N-末端激酶蛋白抑制 Bcl2 基因，从而通过磷脂酶 C 恢复 Ca2+ 稳态，这事件正向调节 Bcl2 以抑制导致 ARVC 的线粒体凋亡。