Interleukin-6 inhibits endothelial nitric oxide synthase activation and increases endothelial nitric oxide synthase binding to stabilized caveolin-1 in human vascular endothelial cells

Hung, Ming‐Jui; Cherng, Wen Jin; Hung, Ming-Yow; Wu, Hsiao Ting; Pang, Jong‐Hwei S.

doi:10.1097/hjh.0b013e32833992ef

Cited by 75 publications

(46 citation statements)

References 34 publications

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“…Thus, incubation with IL-6 (30 ng/mL; concentration within the range produced by PASMCs upon LPS challenge) increased the contractile responses to serotonin, inhibited HPV and reduced the relaxant responses to acetylcholine in isolated PAs, thereby mimicking the effects of LPS. Induction of endothelial dysfunction by IL-6 has been shown in other vascular beds,44 45 through a mechanism involving inhibition of Akt and stabilisation of interactions between endothelial NOS and caveolin 1 46 47. However, in contrast to the effects observed in systemic arteries,48 IL-6 did not reduce the contractile responses to phenylephrine but potentiated those induced by serotonin in isolated rat PAs.…”

Section: Discussionmentioning

confidence: 85%

Role of acid sphingomyelinase and IL-6 as mediators of endotoxin-induced pulmonary vascular dysfunction

Pandolfi

Barreira

Moreno

et al. 2016

Thorax

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Section: Discussionmentioning

confidence: 85%

Role of acid sphingomyelinase and IL-6 as mediators of endotoxin-induced pulmonary vascular dysfunction

Pandolfi

Barreira

Moreno

et al. 2016

Thorax

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“…33, 34 Interleukin-1β and IL-6 disrupt arterial function via generation of reactive oxygen species, 35 and altered eNOS bioactivity. 36 In contrast, microvessels exposed to IL-6 and TNF-α antagonists rescue the abnormal phenotype. 37, 38 Additional, experimental studies further support the growing notion that inflammatory topology of adipose tissue modulates vascular biology.…”

Section: Discussionmentioning

confidence: 99%

Arteriolar Function in Visceral Adipose Tissue Is Impaired in Human Obesity

Farb

Ganley-Leal

Mott

et al. 2012

ATVB

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Objective The purpose of this study was to characterize the relationship between adipose tissue phenotype and depot-specific microvascular function in fat. Methods and Results In 30 obese subjects (age 42±11 yr, BMI 46±11 kg/m2) undergoing bariatric surgery, we intra-operatively collected visceral and subcutaneous adipose tissue and characterized depot-specific adipose phenotypes. We assessed vasomotor function of the adipose microvasculature using videomicroscopy of small arterioles (75–250 μm) isolated from different fat compartments. Endothelium-dependent, acetylcholine-mediated vasodilation was severely impaired in visceral arterioles, compared to the subcutaneous depot (P<0.001 by ANOVA). Non-endothelium dependent responses to papaverine and nitroprusside were similar. Endothelial nitric oxide synthase (eNOS) inhibition with Nω-nitro-L-arginine methyl ester (L-NAME) reduced subcutaneous vasodilation but had no effect on severely blunted visceral arteriolar responses. Visceral fat exhibited greater expression of proinflammatory, oxidative stress-related, hypoxia-induced, and proangiogenic genes; increased activated macrophage populations; and higher capacity for cytokine production ex vivo. Conclusions Our findings provide clinical evidence that the visceral microenvironment may be intrinsically toxic to arterial health providing a potential mechanism by which visceral adiposity burden is linked to atherosclerotic vascular disease. Our findings also support the evolving concept that both adipose tissue quality and quantity may play significant roles in shaping cardiovascular phenotypes in human obesity.

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“…IL-6 directly affects endothelial cells by inducing endothelial cell adhesion molecule expression [23] and inhibiting endothelial nitric oxide synthase (eNOS) activation [24]. Flow-mediated dilation depends upon eNOS activation which is responsible for the synthesis of the endothelium-derived relaxing factor nitric oxide.…”

Section: Discussionmentioning

confidence: 99%

Soluble TNF and IL-6 receptors: Indicators of vascular health in women without cardiovascular disease

et al. 2013

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Cytokine receptor subunits are released from cells in a regulated manner and circulate in soluble forms at concentrations that are orders of magnitude greater than the concentrations of the cytokines themselves. The purpose of this study was to determine if the circulating concentrations of soluble receptor subunits for interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) might serve as early indicators of vascular dysfunction independent of the traditional cardiovascular disease (CVD) risk factors in women. Healthy women, aged 20-50 years (n = 36), were assessed for circulating concentrations of the cytokines IL-1β, IL-6 and TNFα and the soluble cytokine receptor subunits interleukin-1 receptor type I (sIL-1RI), sIL-1RII, sIL-6Rα, glycoprotein 130 (s-gp130), soluble TNF receptor type 1 (sTNFR1), and sTNFR2, along with traditional CVD risk factors. Cytokine receptor subunit expression on mononuclear cells and the release of these subunits in vitro were also determined. Brachial artery flow-mediated dilation (FMD), carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cfPWV) were assessed by ultrasonography and Doppler probes. Circulating sIL-6Rα correlated negatively with FMD (r = −0.56, p = 0.007) independent of age and other CVD risk factors. Circulating sTNFR1 correlated positively with cfPWV (r = 0.60, p = 0.002). TNFR1 receptor expression on monocytes correlated positively with cIMT (r = 0.51, p = 0.004). Plasma concentrations of IL-1β, IL-6 and TNFα were not significantly associated with FMD, cIMT or cfPWV. These data suggest that the receptors for IL-6 and TNFα, rather than the cytokines themselves, may be better indicators of early vascular changes that are associated with CVD.

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Interleukin-6 inhibits endothelial nitric oxide synthase activation and increases endothelial nitric oxide synthase binding to stabilized caveolin-1 in human vascular endothelial cells

Cited by 75 publications

References 34 publications

Role of acid sphingomyelinase and IL-6 as mediators of endotoxin-induced pulmonary vascular dysfunction

Role of acid sphingomyelinase and IL-6 as mediators of endotoxin-induced pulmonary vascular dysfunction

Arteriolar Function in Visceral Adipose Tissue Is Impaired in Human Obesity

Soluble TNF and IL-6 receptors: Indicators of vascular health in women without cardiovascular disease

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