Selective cGAS Inhibition Is Cardioprotective After Myocardial Infarction

Abstract

Activation of the DNA sensor cGAS has emerged as a potential driver of maladaptive inflammation after myocardial infarction. In this study, the authors provide evidence that a newly developed pharmacologic cGAS inhibitor improves cardiac recovery following myocardial infarction. The compound, which can be administered orally, enhanced post-infarct cardiac function and attenuated adverse ventricular dilation. Using spatial transcriptomics, the authors further demonstrate that cGAS inhibition suppresses type I interferon signaling within the infarct border zone, accompanied by reduced expression of stress-associated cardiac remodeling markers such as Nppa. Together, these findings identify cGAS as a therapeutically targetable regulator of post-infarct inflammation and remodeling, and highlight the novelty of an orally bioavailable inhibitor capable of improving cardiac outcomes after myocardial injury.