Cardiac-Specific Deletion Of Socs3 Improved Lipopolysaccharide-Induced Cardiac Dysfunction Via Mitochondria Stabilization

Background: Mechanisms for Lypopolysaccharide (LPS)-induced LV dysfunction is unknown. STAT3 signaling in the heart promotes cardiomyocyte survival during LPS-induced LV dysfunction. In this study, we determined whether STAT3 signaling and its negative regulator SOCS3 would play a role in LPS-induced LV dysfunction. Methods and Results: RT-PCR revealed that gp130 cytokines were markedly increased after LPS injection. Western blot revealed that STAT3 was markedly phosphorylated and SOCS3 was induced in WT mice hearts after LPS injection. To investigate the role of STAT3 and SOCS3, we generated cardiac-specific SOCS3 knockout mice (SOCS3-CKO). LPS (30 mg/kg) impaired cardiac function in both SOCS3-CKO and WT, but the magnitude of cardiac dysfunction was much less in SOCS3-CKO at 6 hr after injection. SOCS3-CKO mice showed the greater survival rate than WT mice after LPS injection. The duration and intensity of STAT3 phosphorylation after LPS injection were greater in SOCS3-CKO mice. The Bcl-xL expression was increased more and the cleaved caspase3 expression was decreased more in SOCS3-CKO mice. Furthermore, expressions of mitochondrial respiratory chain enzyme complex I and II were greater in SOCS3-CKO mice. Conclusion: Our data show that the deletion of SOCS3 in cardiomyocytes may prevent the LPS-induced LV dysfunction in mice via augmenting the STAT3 signaling and stabilizing mitochondria.