Understanding PITX2-dependent Atrial Fibrillation Mechanisms through Computational Models

Jieyun Bai; Yaosheng Lu; Yijie Zhu; Huijin Wang; Dechun Yin; Henggui Zhang; Diego Franco; Jichao Zhao

doi:10.20944/preprints202106.0541.v1

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preprints.org > biology and life sciences > anatomy and physiology > doi: 10.20944/preprints202106.0541.v1

Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Understanding PITX2-dependent Atrial Fibrillation Mechanisms through Computational Models

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Version 1 : Received: 18 June 2021 / Approved: 22 June 2021 / Online: 22 June 2021 (12:32:52 CEST)

A peer-reviewed article of this Preprint also exists.

Bai, J.; Lu, Y.; Zhu, Y.; Wang, H.; Yin, D.; Zhang, H.; Franco, D.; Zhao, J. Understanding PITX2-Dependent Atrial Fibrillation Mechanisms through Computational Models. Int. J. Mol. Sci. 2021, 22, 7681. Bai, J.; Lu, Y.; Zhu, Y.; Wang, H.; Yin, D.; Zhang, H.; Franco, D.; Zhao, J. Understanding PITX2-Dependent Atrial Fibrillation Mechanisms through Computational Models. Int. J. Mol. Sci. 2021, 22, 7681.

Abstract

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 a genetic predisposition to develop AF. Genome-wide association studies have identified genetic variants associated with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene coding for the homeobox transcription PITX2. Because of the inherent complexity of the human heart, experimental and basic research on PITX2-dependent AF is not sufficient for understanding atrial functional proprieties. Linking PITX2 to ion channels, cells, tissues, atria and the whole heart, computational models are necessary for achieving a quantitative understanding of atrial structure and function in PITX2-dependent AF. Computational approaches are used to capture all that we know about PITX2-dependent AF and to develop improved 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.

Keywords

cardiac arrhythmias; atrial fibrillation; PITX2; computational model; electrical remodelling; structural remodelling; calcium handling; mRNA; electrophysiology

Subject

Biology and Life Sciences, Anatomy and Physiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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