Cholesterol catabolism and bile acid synthesis in cardiomyocytes promote inflammation and heart failure

In failing cardiomyocytes, depletion of carnitine acetyltransferase promotes cholesterol catabolism via the bile acid synthesis pathway. The intracellular accumulation of bile acid intermediates induces the release of mitochondrial DNA into the cytosol, triggering type I interferon responses and AIM2 inflammasome activation, thereby contributing to chronic myocardial inflammation and heart failure progression.