Abstract 17498: Cardiac-Specific Thioredoxin-1 Knockout Induces Cardiac Dysfunction

Thioredoxin-1 (Trx1) is a 12 KDa oxidoreductase, which reduces proteins with disulfide bonds through thiol-disulfide exchange reactions. Several lines of evidences show that Trx1 protects cardiomyocytes against stress, such as ischemia and pressure overload. However, due to the embryonic lethality of systemic Trx1 knockout mice, the role of endogenous Trx1 in cardiac function had not been tested with a loss-of-function model. In this study, we generated cardiac-specific Trx1 knockout (Trx1cKO) mice with Trx1floxflox and αMHC-Cre transgenic mice to elucidate the physiological role of Trx1. The protein levels of Trx1 were significantly reduced in Trx1cKO mice in a cardiac-specific manner. The Trx1cKO mice were viable but started dying at 2 weeks of age. The median survival age was 3.6 weeks. None of the mice survived for longer than 8 weeks. Histochemical analyses showed a trend of increased cardiomyocyte cell size in Trx1cKO mice (relative cell size: Wild-type (WT): 1; Trx1cKO: 1.8), whereas apoptotic cell...