Abstract
BackgroundHydrogen sulfide (H2S) has been shown to inhibit the atherosclerosis development and progression. It is produced by cystathionine γ-lyase (CSE) in the cardiovascular system. In our previous study, it has been shown that CSE/H2S system plays a significant role in the changes of uremic accelerated atherosclerosis (UAAS), but the mechanism is not known clearly.MethodsIn this study, we explored the antagonism of CSE/H2S system in UAAS and identified its possible signaling molecules in ApoE−/− mice with 5/6 nephrectomy and fed with atherogenic diet. Mice were divided into sham operation group (sham group), UAAS group, sodium hydrosulfide group (UAAS+NaHS group) and propargylglycine group (UAAS+PPG group). Serum creatinine, urea nitrogen, lipid levels and lesion size of atherosclerotic plaque in the aortic roots were analyzed. Meanwhile, the expression of CSE, TGF-β and phosphorylation of Smad3 were detected.ResultsCompared with sham group, the aortic root of ApoE−/− mice in the UAAS group developed early atherosclerosis, the levels of total cholesterol, triglyceride, low-density lipoprotein-cholesterol, serum creatinine and urea nitrogen were also higher than that in the sham group. NaHS administration can inhibit the development of atherosclerosis, but PPG administration can accelerate the atherosclerosis development. Meanwhile, the protein expression levels of CSE and TGF-β and phosphorylation of Smad3 significantly decreased in the UAAS mice. Treatment of UAAS mice with NaHS inhibited TGF-β protein expression and Smad3 phosphorylation decrease, but PPG treatment had the opposite effect.ConclusionsThe CSE/H2S system is of great importance for treating atherosclerosis in patients with chronic kidney disease, and it may protect the vascular from atherosclerosis through the TGF-β/Smad pathway.
Highlights
Hydrogen sulfide (H2S) has been shown to inhibit the atherosclerosis development and progression
serum creatinine (Scr) and Urea nitrogen (BUN) and levels of lipids were increased in uremic accelerated atherosclerosis (UAAS), UAAS+Sodium hydrosulfide group (NaHS) and UAAS+PPG group mice when compared with sham group mice
Effect of cystathionine γ-lyase (CSE)/H2S system on the size of aortic atherosclerotic plaque To confirm the effect of CSE/H2S system on the aorta, HE staining was used to detect the of aortic atherosclerotic plaque formation
Summary
Hydrogen sulfide (H2S) has been shown to inhibit the atherosclerosis development and progression. It is produced by cystathionine γ-lyase (CSE) in the cardiovascular system. It has been shown that CSE/H2S system plays a significant role in the changes of uremic accelerated atherosclerosis (UAAS), but the mechanism is not known clearly. Extensive atherosclerosis is a well-documented complication of advanced chronic kidney disease (CKD), which is related to a high incidence of cardiovascular events and mortality [1], the contributing factors include inflammation, oxidative stress and blood vascular endothelial cells dysfunction. There are many non-traditional risk factors for atherosclerosis in patients with CKD, such as hyperhomocysteinemia, increased oxidative stress and anemia [5]
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