Angiotensin II downregulates vascular endothelial cell hydrogen sulfide production by enhancing cystathionine γ-lyase degradation through ROS-activated ubiquitination pathway

Aim: Vascular endothelial cell senescence is a leading cause of age-associated diseases and cardiovascular diseases. Interventions and therapies targeting endothelial cell senescence and dysfunction would have important clinical implications. This study was aimed to evaluate the effect of 10 resveratrol analogues, including pterostilbene (Pts) and its derivatives, against endothelial senescence and dysfunction. Methods and Results: All the tested compounds at the concentrations from 10-9 M to 10-6 M did not show cytotoxicity in endothelial cells. Among the 10 resveratrol analogues, Pts and Pts nicotinate attenuated the expression of senescence-associated β-galactosidase, downregulated p21 and p53, and increased the production of NO in both angiotensin II and H2O2-induced endothelial senescence models. In addition, Pts and Pts nicotinate elicited endothelium-dependent relaxations. Pts and Pts nicotinate did not alter Sirtuin 1 (SIRT1) expression but enhanced its activity. Both Pts and Pts nicotinate have high binding activities with SIRT1. Inhibition of SIRT1 by sirtinol reversed the anti-senescent effects of Pts and Pts nicotinate. Conclusions: This study suggests that the Pts and Pts nicotinate ameliorated vascular endothelial senescence and elicited endothelium-dependent relaxations via activation of SIRT1. These two compounds maybe potential drugs for the treatment of cardiovascular diseases related to endothelial senescence and dysfunction.

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Enhanced Sp1/YY1 Expression Directs CBS Transcription to Mediate VEGF-Stimulated Pregnancy-Dependent H 2 S Production in Human Uterine Artery Endothelial Cells

Hypertension ◽

10.1161/hypertensionaha.121.18190 ◽

2021 ◽

Author(s):

Jin Bai ◽

Dong-bao Chen

Keyword(s):

Hydrogen Sulfide ◽

Uterine Artery ◽

Promoter Sequence ◽

Vascular Endothelial ◽

Promoter Activation ◽

Sulfide Production ◽

Hydrogen Sulfide Production ◽

Specificity Protein ◽

Endothelial Growth Factor

Pregnancy and VEGF (vascular endothelial growth factor) stimulate uterine artery endothelial cell (UAEC) hydrogen sulfide production via selectively upregulating CBS (cystathionine β-synthase) but not CSE (cystathionine γ-lyase) expression. This study was conducted to determine the mechanisms by which VEGF utilizes to stimulate pregnancy-dependent upregulation of CBS and hydrogen sulfide production in human UAEC. The proximal human CBS promoter contains 4 Sp1 (specificity protein 1; a/b/c/d) sites and 1 YY1 (Yin Yang 1) site; luciferase assays using reporter genes driven by human CBS promoter with a series of 5′-deletions identified a promoter sequence (−574 to −394) containing Sp1d and the YY1 sites critical for basal and VEGF-stimulated CBS promoter activation. VEGF stimulated pregnancy-dependent recruitment of Sp1 to Sp1d and YY1 to YY1 and also recruited YY1 to Sp1c and increased Sp1/YY1 association in pregnant human UAEC, suggesting formation of a Sp1/YY1 complex at the Sp1c site. Endothelial Sp1 and YY1 proteins were significantly greater in pregnant than nonpregnant human uterine artery. VEGF stimulated pregnancy-dependent Sp1 and YY1 protein expression in vitro. Treatment with Sp1 and YY1 siRNAs completely blocked Sp1/YY1-mediated pregnancy-dependent CBS protein upregulation and hydrogen sulfide production by VEGF in human UAEC. VEGF did not trans -activate CSE promoter or increase CSE expression, and Sp1/YY1 knockdown did not affect CSE expression in human UAEC. Thus, pregnancy augments EC Sp1 and YY1 expression and promotes the recruitment of Sp1/YY1 to their DNA-binding sequences in proximal human CBS promoter to upregulate CBS transcription, underlying a novel mechanism to mediate VEGF-stimulated pregnancy-dependent endothelial hydrogen sulfide production in the human uterine artery.

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Angiotensin II increase the pulmonary metastasis through the vascular endothelial cell adherent pathway in hematogenous metastasis of melanoma cells

Proceedings for Annual Meeting of The Japanese Pharmacological Society ◽

10.1254/jpssuppl.wcp2018.0_po1-8-11 ◽

2018 ◽

Vol WCP2018 (0) ◽

pp. PO1-8-11

Author(s):

Shin Ishikane ◽

Hiroshi Hosoda ◽

Takashi Nojiri ◽

Takeshi Tokudome ◽

Tetsuya Mizutani ◽

...

Keyword(s):

Endothelial Cell ◽

Angiotensin Ii ◽

Pulmonary Metastasis ◽

Vascular Endothelial Cell ◽

Melanoma Cells ◽

Hematogenous Metastasis ◽

Vascular Endothelial

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Pitavastatin maintains MAPK7 expression and alleviates angiotensin II‑induced vascular endothelial cell inflammation and injury

Experimental and Therapeutic Medicine ◽

10.3892/etm.2021.11055 ◽

2021 ◽

Vol 23 (2) ◽

Author(s):

Min Li ◽

Xiaohua Liu

Keyword(s):

Endothelial Cell ◽

Angiotensin Ii ◽

Vascular Endothelial Cell ◽

Vascular Endothelial

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Antioxidant-inhibitable angiotensin II effects on human vascular endothelial cell migration

American Journal of Hypertension ◽

10.1016/s0895-7061(01)01950-1 ◽

2001 ◽

Vol 14 (11) ◽

pp. A149

Author(s):

M Bravi

Keyword(s):

Cell Migration ◽

Endothelial Cell ◽

Angiotensin Ii ◽

Vascular Endothelial Cell ◽

Endothelial Cell Migration ◽

Vascular Endothelial ◽

Human Vascular Endothelial Cell

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Abstract WP100: Hydrogen Sulfide Increases Angiogenesis And Improves Functional Outcome After Stroke

Stroke ◽

10.1161/str.44.suppl_1.awp100 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Mi-Young Oh ◽

Hyunduk Jang ◽

Seung-Hoon Lee ◽

Wi-Sun Ryu ◽

Byung-Woo Yoon

Keyword(s):

Hydrogen Sulfide ◽

Endothelial Cell ◽

Middle Cerebral Artery ◽

Functional Outcome ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Vascular Endothelial Cell ◽

Artery Occlusion ◽

Vascular Endothelial ◽

Cerebral Artery Occlusion

Background: Hydrogen Sulfide is a potent inducer of angiogenesis. In this study, we investigate whether NaHS (H2S donor) induces angiogenesis and thereby improves functional outcome in rat cerebral ischemic/reperfusion model. Methods: Adult male rats were subjected to middle cerebral artery occlusion and were treated with 5mg/kg of NaHS or normal saline starting 48 hours after middle cerebral artery occlusion and daily for 14 days. Neurological functional tests were performed. The volume of von willebrand factor(vWF)- positive area was measured. Newly proliferated vascular endothelial cell were counted. Angiogenic factor expressions were measured by immunohistochemistry and western blot. In vitro, endothelial tube formation was examined. Result: NaHS significantly promoted vWF-positive area (30.1±10.1% vs. vehicle, 12.3±7.1 %, p<0.01) and proliferation of vascular endothelial cell (7.3/2*105 um2 vs. vehicle, 3.1/2*105um2, p<0.01) in the ischemic brain. and improved functional outcome after stroke. Mechanisms underlying the NaHS-induced vascular remodeling were investigated. NaHS increased the expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang1), angiopoietin-2(Ang-2) and phosphorylation of Akt, and ERK-1/2. Conclusions: NaHS promoted angiogenesis, which may contribute to improvement of functional outcome after stroke. The VEGF/VEGF receptor, phosphoinositide 3-kinase/Akt, and ERK-1/2 pathways appear to mediate NaHS-induced angiogenesis.

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