Atrial fibrillation (AF) is the most common heart arrhythmia, in which atria contract rapidly and irregularly and the contraction of atria and ventricles is no longer coordinated. Current guidelines for the treatment of AF recommend medication to avoid blood clotting and stroke, control heart rate, and restore sinus rhythm. However, the available treatments show limited efficiency and may have side effects associated with increased morbidity and mortality, emphasizing an urgent need for new therapies.
In a recent study in Cell Reports Medicine, Lal et al. suggest that metformin, the drug of choice for the oral treatment of type 2 diabetes, may be repurposed for the treatment of AF. The researchers first generated an AF disease module by combining RNA-sequencing data from the left atria of 251 patients with AF who underwent elective cardiac surgery and 14 non-failing donor hearts with a published human protein–protein interactome. The AF disease module provided a network of hundreds of proteins that could represent potential drug targets for AF. The authors generated a drug target network from 2,891 approved and clinically explored drugs obtained from the Drugbank and Therapeutic Target (TTD) databases. By calculating the network proximity of drug targets to the AF disease module, followed by gene expression analysis of drug-treated human cell lines from the Connectivity Map database, the researchers identified nine potentially repurposable drugs, with the AMPK agonists phenformin and metformin as top hits. Because a previous prospective case–control study showed that individuals treated with metformin have a 19% decrease in the incidence of new-onset AF, the scientists focused on metformin as a potential drug to treat AF.
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