Salusin-β contributes to oxidative stress and inflammation in diabetic cardiomyopathy

Salusin-beta accelerates inflammatory responses in vascular endothelial cells, and increases oxidative stress in vascular smooth muscle cells. Plasma salusin-beta levels were increased in diabetic patients. This study was designed to determine whether salusin-beta is involved in the pathogenesis of diabetic cardiomyopathy (DCM), and whether knockdown of salusin-beta attenuates cardiac inflammation and oxidative stress in rats with DCM. H9c2 or neonatal rat cardiomyocytes were incubated with 33.3 mM of glucose to mimic the high glucose (HG) in diabetes. Streptozotocin and high-fat diet were used to induce type 2 diabetes in rats. HG induced salusin-beta expression in H9c2 cells. Salusin-beta caused greater responses of oxidative stress, NF kappa B activation and inflammation in HG-treated H9c2 cells than these in control H9c2 cells. Diphenyleneiodonium (a NAD(P)H oxidase inhibitor) or N-acetylcysteine (an antioxidant) inhibited the salusin-beta-induced NF kappa B activation and inflammation. Bay11-7082 (a NF kappa B inhibitor) attenuated salusin-beta-induced inflammation but not oxidative stress. Knockdown of salusin-beta prevented the HG-induced oxidative stress, NF kappa B activation and inflammation in neonatal rat cardiomyocytes. Silencing salusin-beta with adenoviruse-mediated shRNA had no significant effects on blood glucose and insulin resistance, but attenuated ventricular dysfunction in diabetic rats. Oxidative stress, NF kappa B activation, inflammation, salusin-beta upregulation in myocardium of diabetic rats were prevented by knockdown of salusin-beta. These results indicate that salusin-beta contributes to inflammation in DCM via NOX2/ROS/NF kappa B signaling, and that knockdown of salusin-beta attenuates cardiac dysfunction, oxidative stress and inflammation in DCM.