Stromal interaction molecule 1 modulates blood pressure via NO production in vascular endothelial cells

2018 ◽  
Vol 41 (7) ◽  
pp. 506-514 ◽  
Author(s):  
Mitsuhiro Nishimoto ◽  
Risuke Mizuno ◽  
Toshiro Fujita ◽  
Masashi Isshiki
Keyword(s):  
Blood Pressure ◽  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
No Production ◽  
Vascular Endothelial ◽  
Stromal Interaction Molecule 1

Hydroxytyrosol NO regulates oxidative stress and NO production through SIRT1 in diabetic mice and vascular endothelial cells

Phytomedicine ◽  
2019 ◽  
Vol 52 ◽  
pp. 206-215 ◽  
Author(s):  
Weirong Wang ◽  
Chenxu Shang ◽  
Wei Zhang ◽  
Zhen Jin ◽  
Feng Yao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
No Production ◽  
Vascular Endothelial ◽  
Diabetic Mice

Abstract 153: Bile Acid Receptor TGR5 Agonism Represents Anti-inflammatory Effects via Stimulating Nitric Oxide Production in Vascular Endothelial Cells

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Taiki Kida ◽  
Yoshiki Tsubosaka ◽  
Masatoshi Hori ◽  
Hiroshi Ozaki ◽  
Takahisa Murata
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Bile Acids ◽  
Inflammatory Responses ◽  
Vascular Endothelial Cells ◽  
Lithocholic Acid ◽  
Signal Pathways ◽  
No Production ◽  
Vascular Endothelial ◽  
Anti Inflammatory

Objective TGR5, a membrane-bound, G-protein-coupled receptor for bile acids, is known to be involved in regulation of energy homeostasis and inflammation. However, little is known about the function of TGR5 in vascular endothelial cells. In the present study, we examined whether TGR5 agonism represents anti-inflammatory effects in vascular endothelial cells focusing on nitric oxide (NO) production. Methods and Results In human umbilical vein endothelial cells (HUVECs), treatment with taurolithocholic acid (TLCA), which has the highest affinity to TGR5 among various bile acids, significantly reduced tumor necrosis factor (TNF)-α-induced vascular cell adhesion molecule (VCAM)-1 protein expression and adhesion of human monocytes, U937. These effects were abrogated by a NO synthase (NOS) inhibitor, N G -Monomethyl-L-arginine (L-NMMA). In bovine aortic endothelial cells (BAECs), treatment with TLCA as well as lithocholic acid, which also has high affinity to TGR5, significantly increased the NO production. In contrast, deoxycholic acid and chenodeoxycholic acid, which possess low affinity to TGR5, did not affect the NO production. Gene depletion of TGR5 by siRNA transfection abolished TLCA-induced NO production in BAECs. TLCA-induced NO production was also observed in HUVECs measured as intracellular cGMP accumulation. We next investigated the signal pathways responsible for the TLCA-induced NO production in endothelial cells. Treatment with TLCA increased endothelial NOS (eNOS) ser1177 phosphorylation in HUVECs. This response was accompanied by increased Akt ser473 phosphorylation and intracellular Ca 2+ ([Ca 2+ ] i ). Treatment with phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or blockade of calcium channel with La 3+ , significantly decreased TLCA-induced eNOS ser1177 phosphorylation and subsequent NO production. Conclusion These results indicate that TGR5 agonism can mediate anti-inflammatory responses by suppressing VCAM-1 expression and monocytes adhesion to endothelial cells. This function is dependent on NO production via Akt activation and [Ca 2+ ] i increase.

scholarly journals VE-PTP inhibition elicits eNOS phosphorylation to blunt endothelial dysfunction and hypertension in diabetes

2020 ◽  
Author(s):  
Mauro Siragusa ◽  
Alberto Fernando Oliveira Justo ◽  
Pedro Felipe Malacarne ◽  
Anna Strano ◽  
Akshay Buch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Dysfunction ◽  
Vascular Reactivity ◽  
Therapeutic Option ◽  
Diabetic Patients ◽  
No Production ◽  
Vascular Endothelial ◽  
Enos Activity

Abstract Aims Receptor-type vascular endothelial protein tyrosine phosphatase (VE-PTP) dephosphorylates Tie-2 as well as CD31, VE-cadherin, and vascular endothelial growth factor receptor 2 (VEGFR2). The latter form a signal transduction complex that mediates the endothelial cell response to shear stress, including the activation of the endothelial nitric oxide (NO) synthase (eNOS). As VE-PTP expression is increased in diabetes, we investigated the consequences of VE-PTP inhibition (using AKB-9778) on blood pressure in diabetic patients and the role of VE-PTP in the regulation of eNOS activity and vascular reactivity. Methods and results In diabetic patients AKB-9778 significantly lowered systolic and diastolic blood pressure. This could be linked to elevated NO production, as AKB increased NO generation by cultured endothelial cells and elicited the NOS inhibitor-sensitive relaxation of endothelium-intact rings of mouse aorta. At the molecular level, VE-PTP inhibition increased the phosphorylation of eNOS on Tyr81 and Ser1177 (human sequence). The PIEZO1 activator Yoda1, which was used to mimic the response to shear stress, also increased eNOS Tyr81 phosphorylation, an effect that was enhanced by VE-PTP inhibition. Two kinases, i.e. abelson-tyrosine protein kinase (ABL)1 and Src were identified as eNOS Tyr81 kinases as their inhibition and down-regulation significantly reduced the basal and Yoda1-induced tyrosine phosphorylation and activity of eNOS. VE-PTP, on the other hand, formed a complex with eNOS in endothelial cells and directly dephosphorylated eNOS Tyr81 in vitro. Finally, phosphorylation of eNOS on Tyr80 (murine sequence) was found to be reduced in diabetic mice and diabetes-induced endothelial dysfunction (isolated aortic rings) was blunted by VE-PTP inhibition. Conclusions VE-PTP inhibition enhances eNOS activity to improve endothelial function and decrease blood pressure indirectly, through the activation of Tie-2 and the CD31/VE-cadherin/VEGFR2 complex, and directly by dephosphorylating eNOS Tyr81. VE-PTP inhibition, therefore, represents an attractive novel therapeutic option for diabetes-induced endothelial dysfunction and hypertension.

Angiotensin II receptor blockade corrects altered expression of gap junctions in vascular endothelial cells from hypertensive rats

2004 ◽  
Vol 287 (1) ◽  
pp. H216-H224 ◽  
Author(s):  
Yasuo Kansui ◽  
Koji Fujii ◽  
Keiichiro Nakamura ◽  
Kenichi Goto ◽  
Hideyuki Oniki ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Gap Junctions ◽  
Vascular Endothelial Cells ◽  
Renin Angiotensin System ◽  
Vascular Endothelial ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Renin Angiotensin

Blockade of the renin-angiotensin system improves the impaired endothelium-dependent relaxations associated with hypertension and aging, partly through amelioration of endothelium-derived hyperpolarizing factor (EDHF)-mediated responses. Although the nature of EDHF is still controversial, recent studies have suggested the involvement of gap junctions in EDHF-mediated responses. Gap junctions consist of connexins (Cx), and we therefore tested whether the expression of Cx in vascular endothelial cells would be altered by hypertension and antihypertensive treatment. Spontaneously hypertensive rats (SHR) were treated with either the angiotensin II type 1 receptor antagonist candesartan or the combination of hydralazine and hydrochlorothiazide for 3 mo from 5 to 8 mo of age. Confocal laser scanning microscopy after immunofluorescent labeling with antibodies against Cx37, Cx40, and Cx43 revealed that the expression of Cx37 and Cx40 in endothelial cells of the mesenteric artery was significantly lower in SHR than in WKY. Treatment with candesartan, but not the combination of hydralazine and hydrochlorothiazide, significantly increased the expression of Cx37 and Cx40, although blood pressure decreased similarly. On the other hand, the expression of Cx43, though scarce and heterogeneous, was increased in SHR compared with WKY, and candesartan treatment lowered the expression of Cx43. These findings suggest that renin-angiotensin system blockade corrects the decreased expression of Cx37 and Cx40 in arterial endothelial cells of hypertensive rats, partly independently of blood pressure, whereas the expression of Cx43 changed in the opposite direction. It remains to be clarified whether these changes in Cx37 and Cx40 are related to endothelial function, particularly that attributable to EDHF.

scholarly journals Black soybean seed coat polyphenols promote nitric oxide production in the aorta through the Akt/eNOS pathway

2020 ◽  
Vol 10 (8) ◽  
pp. 330
Author(s):  
Chiaki Domae ◽  
Hitoshi Ashida ◽  
Yoko Yamashita
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Seed Coat ◽  
Vascular Endothelial Cells ◽  
Soybean Seed ◽  
No Production ◽  
Vascular Endothelial ◽  
Intestinal Epithelial ◽  
Black Soybean ◽  
Soybean Seed Coat

Background: Black soybean seed coat contains an abundance of flavan-3-ols and possesses various bioregulatory functions. Nitric oxide (NO) is produced by endothelial nitric oxide synthase (eNOS) in vascular endothelial cells and regulates vascular function through vasodilation and the inhibition of platelet aggregation in blood vessels. It has been reported that flavan-3-ols increase NO production, but many previous reports used a high concentration of flavan-3-ols. In the present study, we investigated the effect of flavan-3-ol-rich black soybean seed coat extract (BE) on NO production at a lower concentration that is close to the concentration after permeation through the monolayer of Caco-2 cells.Methods: Human umbilical vein endothelial cells (HUVEC) were incubated with BE, and then NO production in the medium and eNOS phosphorylation in the cells were examined. Intestinal epithelial Caco-2 cells on the upper side of a transwell filter were co-cultured with HUVEC on the basolateral compartment of the transwell apparatus. BE was added from the upper side, and the basolateral medium was collected to measure the concentration of NO and the content of flavan-3-ols. Furthermore, HUVEC were incubated with each flavan-3-ol in order to individuate the most effective compound in BE.Results: BE significantly increased NO production in the medium of HUVEC. When polyphenols in BE were removed from the basolateral medium by ethyl acetate extraction, increased NO production from HUVEC was not observed. Additionally, BE increased phosphorylation of eNOS and Akt in HUVEC. A portion of flavan-3-ols in BE had permeated through intestinal epithelial cells. Among the flavan-3-ols that had permeated, procyanidin C1 had the strongest effect on NO production in HUVEC at the concentration that had permeated the monolayer of Caco-2 cells. Procyanidin C1 (0.05 µM) also induced phosphorylation of eNOS and Akt in HUVEC without affecting the cAMP level. Conclusion: A portion of flavan-3-ols in BE directly promoted NO production through the Akt/eNOS pathway in vascular endothelial cells. These findings suggest that flavan-3-ols in the black soybean seed coat may contribute to improve the vascular function.Keywords: Black soybean seed coat polyphenols; NO; eNOS; Akt; vascular endothelial cells

Regulation of nitric oxide synthesis by oxygen in vascular endothelial cells

1997 ◽  
Vol 272 (6) ◽  
pp. L1161-L1166 ◽  
Author(s):  
A. R. Whorton ◽  
D. B. Simonds ◽  
C. A. Piantadosi
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Oxidation Products ◽  
No Oxidation ◽  
No Production ◽  
Vascular Endothelial ◽  
Intact Cells ◽  
Aortic Endothelial Cells ◽  
Basal Rate

Vascular endothelial cells synthesize nitric oxide (NO) in response to agonists that elevate cytosolic free Ca2+ concentrations. Once activated, NO synthase (NOS) requires arginine, NADPH, and O2 as cosubstrates. In this study, we investigated the role of O2 in regulating endothelial NOS activity in intact bovine aortic endothelial cells by measuring the rate of nitrite (NO2-) and nitrate (NO3-) production after conversion of NO2- to S-nitrosoglutathione before analysis or after reduction of NO2- and NO3- to NO using acidic vanadium chloride. The basal rate of NO2- production was 6.5 +/- 0.8 pmol.min-1.mg protein-1. Thapsigargin (TG, 1 microM) elevated free cytosolic Ca2+ concentration and increased the rate of NO2- synthesis. At maximal concentrations of TG, the rate of stimulated NO2- production was linear for at least 20 min and was eightfold higher than the basal rate (53.5 +/- 1.8 pmol.min-1.mg protein-1). Incubation of cells in gas mixtures chosen to produce PO2 values in the physiological range led to a progressive fall in the rate of TG-stimulated NO2- production, as O2 concentrations were reduced from that of room air. The half-maximal effective concentration for NO2- production by intact cells was found to occur at 38 Torr. PO2 values higher than that of room air did not lead to a change in the rate of TG-stimulated NO2- production. To confirm that measurement of NO2- accurately reflects total NO production, both NO2- plus NO3- were measured in buffer samples from cells incubated in either room air or N2. The sum of these NO oxidation products was inhibited similarly by hypoxia. These findings suggest that O2 is an important determinant of NOS activity in hypoxic tissues or in vascular beds such as the pulmonary arterial or fetal circulation where PO2 values in the range of 40 Torr are encountered normally.

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