Flavin Adenine Dinucleotide Ameliorates Pressure Overload-Induced Heart Failure by Activating the Short-Chain Acyl-CoA Dehydrogenase.

Flavin adenine dinucleotide (FAD), a cofactor that catalyzes the reaction of flavin protein, participates in fatty acid β-oxidation, which has been shown to inhibit pathological cardiac hypertrophy and fibrosis in spontaneously hypertensive rats. However, the therapeutic advantage of FAD for heart failure (HF) treatment has not been investigated. This study aimed to explore the effects and underlying mechanisms of FAD in a transverse aortic constriction-induced HF mouse model and in vitro tert-butyl hydroperoxide (tBHP)-induced cardiomyocyte apoptosis model experiments. FAD considerably inhibited tBHP-induced cardiomyocyte apoptosis. In addition, FAD significantly increased the activity and expression of the short-chain acyl-CoA dehydrogenase enzyme and adenosine triphosphate (ATP) content while reducing the content of free fatty acids and reactive oxygen species both in vitro and in vivo. Meanwhile, FAD increased the mitochondrial membrane potential, suppressed mitochondrial membrane swelling, and decreased myocardial fibrosis and TUNEL-positive apoptosis cells in the TAC-induced HF mice. In conclusion, our results indicate that FAD plays a positive role in preventing and treating HF, which can be attributed in part to the activation of short-chain acyl-CoA dehydrogenase.