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Petri Net modelling approach for analysing the behaviour of Wnt/[inline-formula removed]-catenin and Wnt/Ca2+ signalling pathways in arrhythmogenic right ventricular cardiomyopathy.

Abstract
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.
AuthorsNazia Azim, Jamil Ahmad, Nadeem Iqbal, Amnah Siddiqa, Abdul Majid, Javaria Ashraf, Fazal Jalil
JournalIET systems biology (IET Syst Biol) Vol. 14 Issue 6 Pg. 350-367 (12 2020) ISSN: 1751-8857 [Electronic] England
PMID33399099 (Publication Type: Journal Article)
Topics
  • Arrhythmogenic Right Ventricular Dysplasia (pathology)
  • Calcium Signaling
  • Models, Cardiovascular
  • Stochastic Processes
  • Wnt Signaling Pathway

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