Disruption or inhibition of 12/15-LOX improved STZ-induced cardiac dysfunction and fibrosis by reducing inflammation and oxidative stress in diabetic mice.
Does inhibition or deletion of 12/15-LOX improve cardiac dysfunction and fibrosis in models of diabetic cardiomyopathy?
Inhibition of 12/15-LOX reduces inflammation and oxidative stress, improving cardiac dysfunction and fibrosis in preclinical models of diabetic cardiomyopathy.
Diabetes affects cardiac structure and function, and it has been suggested that diabetes leads to cardiomyopathy. Arachidonate 12/15-lipoxygenase (LOX) has been suggested to play an important role in atherogenesis and heart failure. However, the role of 12/15-LOX in diabetic cardiomyopathy has not been examined. In this study, we investigated the effects of cardiac 12/15-LOX on diabetic cardiomyopathy. We created streptozotocin (STZ)-induced diabetic mice and compared them with Alox15-deficient mice. Expression of 12/15-LOX and inflammatory cytokines such as tumor necrosis factor (TNF)-α and nuclear factor (NF)-κB were upregulated in STZ-induced diabetic hearts. Disruption of 12/15-LOX significantly improved STZ-induced cardiac dysfunction and fibrosis. Moreover, deletion of 12/15-LOX inhibited the increases of TNF-α and NF-κB as well as the production of STZ-induced reactive oxygen species in the heart. Administration of N-acetylcysteine in diabetic mice prevented STZ-induced cardiac fibrosis. Neonatal cultured cardiomyocytes exposed to high glucose conditions induced the expression of 12/15-LOX as well as TNF-α, NF-κB, and collagen markers. These increases were inhibited by treatment of the 12/15-LOX inhibitor. Our results suggest that cardiac 12/15-LOX-induced inflammation and oxidative stress are involved in the development of diabetic cardiomyopathy and that inhibition of 12/15-LOX could be a novel treatment for this condition.
Suzuki et al. (Tue,) conducted a other in Diabetic cardiomyopathy. 12/15-LOX disruption or inhibition vs. Wild-type STZ-induced diabetic mice or untreated controls was evaluated on Cardiac dysfunction, fibrosis, inflammation, and oxidative stress. Disruption or inhibition of 12/15-LOX improved STZ-induced cardiac dysfunction and fibrosis by reducing inflammation and oxidative stress in diabetic mice.