Understanding PITX2-Dependent Atrial Fibrillation Mechanisms through Computational Models

Atrial fibrillation (AF) is a common arrhythmia. Better prevention and treatment of AF are needed to reduce AF-associated morbidity and mortality. Several major mechanisms cause AF in patients, including genetic predispositions to AF development. Genome-wide association studies have identified a number of genetic variants in association with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene for the homeobox transcription PITX2. Because of the inherent complexity of the human heart, experimental and basic research is insufficient for understanding the functional impacts of PITX2 variants on AF. Linking PITX2 properties to ion channels, cells, tissues, atriums and the whole heart, computational models provide a supplementary tool for achieving a quantitative understanding of the functional role of PITX2 in remodelling atrial structure and function to predispose to AF. It is hoped that computational approaches incorporating all we know about PITX2-related structural and electrical remodelling would provide better understanding into its proarrhythmic effects leading to development of improved anti-AF therapies. In the present review, we discuss advances in atrial modelling and focus on the mechanistic links between PITX2 and AF. Challenges in applying models for improving patient health are described, as well as a summary of future perspectives.

Citation

International Journal of Molecular Sciences, volume 22, issue 14, page e7681

Publisher

MDPI

URI

http://hdl.handle.net/10034/625338

Type

article

Description

From MDPI via Jisc Publications Router
History: accepted 2021-07-16, pub-electronic 2021-07-19
Publication status: Published
Funder: National Key Research and Development Program of China; Grant(s): 2019YFC0120100, 2019YFC0121907
Funder: National Natural Science Foundation of China; Grant(s): 61901192