Determinants and therapeutic potential of calcium handling abnormalities in atrial fibrillation: what can we learn from computer models?

Atrial Fibrillation and Lifestyle Modification: Charting New Courses for Cardiovascular Health

“…A holistic understanding of atrial fibrillation (AF) etiology requires considering factors beyond electrophysiology. Genetic predisposition, inflammatory processes, and lifestyle factors all play a role in shaping the trajectory of AF [25][26][27][28]. Electrophysiological abnormalities alone may not provide a complete picture of AF etiology, and a comprehensive approach is needed to unravel the complex interplay between these factors.…”

Deciphering calcium signals in cells and tissues with tailored probes and models

“…Overall, the review demonstrates the enormous potential of combining mathematical modelling with multiplexed recordings of biochemical activities to discover complex regulatory networks. Readers interested in the translational implications of computational models of complex Ca 2+ signals should not miss the two back-to-back papers by Zhang et al in The Journal of Physiology , as discussed in Heijman & Dobrev (2022). Their three-dimensional models of human atrial cardiomyocytes replicate a wide range of morphological alterations associated with pro-arrhythmic Ca 2+ signals and can predict the effects of anti-arrhythmic Pan and Garaschuk (2022) discusses the role of calcium signals in sensing environmental damage to control the effector function of mouse brain microglia.…”

“…Readers interested in the translational implications of computational models of complex Ca 2+ signals should not miss the two back‐to‐back papers by Zhang et al. in The Journal of Physiology (Zhang, Ni et al., 2022; Zhang, Smith et al., 2022), as discussed in Heijman & Dobrev (2022). Their three‐dimensional models of human atrial cardiomyocytes replicate a wide range of morphological alterations associated with pro‐arrhythmic Ca 2+ signals and can predict the effects of anti‐arrhythmic strategies at different stages of ultrastructural remodelling.…”

Cell diversity and signalling in the cardiovascular system

“…This is an area of active investigation in the field, as the cardiac cell ultrastructure has been shown to play a critical role in the propagation of electrical signals in the heart and in the regulation of calcium handling and contraction during cardiac development (Manfra et al., 2023), normal function and pathophysiology. An accompanying editorial highlights quantitative and modelling approaches as essential to address several unresolved questions about the relative importance of various mechanisms involved in cardiac disease arrhythmia and their suitability as antiarrhythmic targets (Heijman & Dobrev, 2023). The notion that structural and electrophysiological remodelling are intricately linked is also nicely demonstrated in a recent paper in The Journal elucidating the role of cardiac fibrotic remodelling in repolarization heterogeneity and ventricular arrhythmia risk in aged spontaneously hypertensive rats (Khwaounjoo et al., 2022).…”