AUTHOR=Lu Xiangxue , Li Han , Wang Shixiang 

TITLE=Hydrogen Sulfide Protects Against Uremic Accelerated Atherosclerosis via nPKCδ/Akt Signal Pathway

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=7

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2020.615816

DOI=10.3389/fmolb.2020.615816

ISSN=2296-889X

ABSTRACT=<p><bold>Background:</bold> Cardiovascular disease is the most common complication and leading cause of death in maintenance hemodialysis patients. Previous studies have found that disorders of cystathionine-gamma-lyase/hydrogen sulfide (CSE/H<sub>2</sub>S) system in maintenance hemodialysis patients are correlated with the risk of cardiovascular disease. Although the role of CSE/H<sub>2</sub>S system in UAAS has been preliminarily explored, the molecular mechanism of CSE/H<sub>2</sub>S is still not systematically elaborated, and the molecular mechanism of nPKCδ and its related signaling pathway in UAAS is still not thoroughly studied.</p><p><bold>Methods:</bold> Forty chronic kidney disease (CHD) patients were studied and the activation of nPKCδ in peripheral blood mononuclear cells (PBMCs) were detected. ApoE<sup>−/−</sup> mice aged 6 weeks were treated with 5/6 nephrectomy and high-fat diet to make UAAS model. They were divided into Sham group (Sham group), UAAS group (UAAS group), UAAS+L-cysteine group (UAAS+L-cys group), UAAS+sodium hydrosulfide group (UAAS+NaHS group) and UAAS+propargylglycine group (UAAS+PPG group). The UAAS+L-cys group, UAAS+NaHS group and UAAS+PPG group were respectively given L-cys, NaHS and PPG by intraperitoneal injection. The aorta was taken 6 weeks after surgery. Western blot was used to detect the activation of nPKCδ, the phosphorylation of Akt, and the expression of VCAM-1 in the aorta of mice.</p><p><bold>Results:</bold> The membrane translocation of nPKCδ in CHD patients with plaque was higher than that in CHD patients without plaque. The membrane translocation of nPKCδ and the expression of VCAM-1 in UAAS group was higher than sham group, L-cys or NaHS injection could suppress the membrane translocation of nPKCδ and the expression of VCAM-1, but PPG treatment resulted in more membrane translocation of nPKCδ and the expression of VCAM-1 (<italic>P</italic>&lt;0.05, n=6 per group). Akt phosphorylation in UAAS group was lower than sham group, and L-cys or NaHS injection could suppress the degradation of Akt phosphorylation, but PPG treatment resulted in more decrease in the Akt phosphorylation (<italic>P</italic>&lt;0.05, n=6 per group).</p><p><bold>Conclusion:</bold> Endogenous CSE/H<sub>2</sub>S system protected against the formation of UAAS via nPKCδ/Akt signal pathway. The imbalance of CSE/H<sub>2</sub>S system may participate in the formation of UAAS by affecting the expression of downstream molecule VCAM-1, which may be mediated by nPKCδ/Akt signaling pathway.</p>