Key result
Administration of H2S donors (NaHS and GYY4137) inhibited hyperglycemia-induced cardiac fibrosis, NOX4 expression, and ROS production in experimental models of diabetic cardiomyopathy.
Why the study?
Does exogenous hydrogen sulfide attenuate cardiac fibrosis in experimental models of diabetic cardiomyopathy?
Does exogenous hydrogen sulfide attenuate cardiac fibrosis in experimental models of diabetic cardiomyopathy?
Exogenous hydrogen sulfide attenuates cardiac fibrosis in diabetic cardiomyopathy models by targeting NOX4 and regulating ROS-ERK1/2-MAPkinase pathways.
Answers are grounded in this paper and cite their sources.
Supports H2S modulation in diabetic cardiomyopathy models; hypothesis-generating and requires human validation before clinical consideration.
BACKGROUND: Oxidative stress inducing hyperglycemia and high glucose play an important role in the development of cardiac fibrosis associated with diabetic cardiomyopathy. The endogenous gasotransmitter hydrogen sulfide (H2S) can act in a cytoprotective manner. However, whether H2S could inhibit the fibrotic process is unclear. The purpose of our study was to examine the role of H2S in the development and underlying mechanisms behind diabetic cardiomyopathy. METHODS: Diabetic cardiomyopathy was induced in rats by injection of streptozotocin (STZ). Cardiac fibrosis and proliferation of rat neonatal cardiac fibroblasts were induced by hyperglycemia and high glucose. We tested the effects of GYY4137 (a slow-releasing H2S donor), NaHS (an exogenous H2S donor) and NADPH oxidase 4 (NOX4) siRNA on reactive oxygen species (ROS) production, MMP-2,9, cystathionine-γ-lyase (CSE), NOX4, and extracellular signal-regulated kinase 1/2 (ERK1/2) to reveal the effects of H2S on the cardiac fibrosis of diabetic cardiomyopathy. RESULT: In vivo, NaHS treatment inhibited hyperglycemia-induced expression of type I and III collagen, MMP-2 and MMP-9 in diabetic hearts. Rat neonatal cardiac fibroblast migration and cell survival were inhibited by administration of GYY4137. NOX4 expression was increased by hyperglycemia and high glucose, but was reduced in cardiac fibroblasts treated by NaHS and GYY4137. ROS production, ERK1/2 phosphorylation and MMP-2 and 9 expression were decreased in rat neonatal cardiac fibroblasts treated with GYY4137 and NOX4 siRNA. CONCLUSION: The present study shows that enhanced NOX4 expression results in cardiac fibrosis through ROS-ERK1/2-MAPkinase-dependent mechanisms in diabetic cardiomyopathy. NOX4 could be an important target for H2S to regulate redox homeostasis in cardiac fibrosis of diabetic cardiomyopathy.
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Zheng et al. (2015) studied Diabetic cardiomyopathy and cardiac fibrosis. H2S donors (GYY4137, NaHS) vs. Hyperglycemia/high glucose without treatment was evaluated on Cardiac fibrosis, ROS production, NOX4 expression, and MMP-2/9 expression. Administration of H2S donors (NaHS and GYY4137) inhibited hyperglycemia-induced cardiac fibrosis, NOX4 expression, and ROS production in experimental models of diabetic cardiomyopathy.
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