AI Article Synopsis

  • Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a genetic heart disease that leads to fatty tissue replacing muscle in the right ventricle, increasing the risk of arrhythmias and sudden cardiac death.
  • The study introduces a mathematical model to better understand how ARVC affects heart structure and how cardiac cells change identity, focusing on pathways like Wnt/β-catenin and RhoA-ROCK.
  • The findings suggest that for ARVC to develop, both Wnt/β-catenin and RhoA-ROCK pathways need to be inactive, indicating a complex interaction that might contribute to the disease's progression.

Article Abstract

Arrhythmogenic Right Ventricular cardiomyopathy (ARVC) is an inherited cardiac muscle disease linked to genetic deficiency in components of the desmosomes. The disease is characterized by progressive fibro-fatty replacement of the right ventricle, which acts as a substrate for arrhythmias and sudden cardiac death. The molecular mechanisms underpinning ARVC are largely unknown. Here we propose a mathematical model for investigating the molecular dynamics underlying heart remodeling and the loss of cardiac myocytes identity during ARVC. Our methodology is based on three computational models: firstly, in the context of the Wnt pathway, we examined two different competition mechanisms between β-catenin and Plakoglobin (PG) and their role in the expression of adipogenic program. Secondly, we investigated the role of RhoA-ROCK pathway in ARVC pathogenesis, and thirdly we analyzed the interplay between Wnt and RhoA-ROCK pathways in the context of the ARVC phenotype. We conclude with the following remark: both Wnt/β-catenin and RhoA-ROCK pathways must be inactive for a significant increase of expression, suggesting that a crosstalk mechanism might be responsible for mediating ARVC pathogenesis.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923182PMC
http://dx.doi.org/10.3390/ijms22042004DOI Listing

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