EP Fellows Curriculum: Molecular Mechanisms Underlying Atrial Fibrillation - Implications for New Gene Based Therapies-EP Fellows Curriculum: Molecular Mechanisms Underlying Atrial Fibrillation - Implications for New Gene Based Therapies

Video Transcription

Video Summary

Dr. Rishi Arora's video presentation on atrial fibrillation (AFib) discusses the molecular mechanisms underlying the condition and highlights potential gene-based therapies for targeted treatment. He begins by explaining that AFib is a common heart rhythm disorder and that current treatments are not focused on the underlying causes of the disease.<br /><br />Dr. Arora focuses on the autonomic nervous system's role in AFib and the remodeling that occurs in the atrial nerves. His research demonstrates that parasympathetic and sympathetic nerves play a significant role in initiating and maintaining AFib.<br /><br />Fibrosis, characterized by scar tissue accumulation, is also discussed as an important factor in AFib. Dr. Arora's research aims to understand the molecular pathways involved in fibrosis and develop gene-based therapies to target these pathways.<br /><br />One potential therapy mentioned is disrupting the signaling protein G-alpha-i2, which reduces parasympathetic signaling and AFib. Dr. Arora also explores the role of nerve growth factor in atrial remodeling and its potential as a therapeutic target.<br /><br />The talk emphasizes the importance of understanding the molecular mechanisms of AFib and the potential for gene-based therapies to provide more effective and targeted treatments.<br /><br />The other video transcript focuses on the role of TGF-beta-1, oxidative stress, and electrophoretic ablation in treating AFib. Dr. Arora explains that TGF-beta-1 is a signaling molecule that increases fibrosis and that targeting its signaling can improve heart conduction. He also discusses the role of oxidative stress in AFib and its contribution to electrical and structural remodeling. Dr. Arora suggests that targeting TGF-beta signaling and oxidative stress through gene-based therapies could be effective in treating AFib.<br /><br />He further explores the use of electroporation, a technique that uses electrical currents to deliver genes, as a method to overexpress or knock out specific genes involved in AFib. The limitations of current ablation strategies are also mentioned, and Dr. Arora suggests targeting electrograms that reflect the true underlying AFib substrate.<br /><br />Overall, Dr. Arora emphasizes the importance of understanding the underlying mechanisms of AFib to develop more effective treatment approaches.

Keywords

Atrial fibrillation

AFib

Molecular mechanisms

Gene-based therapies

Autonomic nervous system

Atrial nerves

Fibrosis

G-alpha-i2

Nerve growth factor

TGF-beta-1