Age-associated impairment in vasorelaxation to fluid shear stress in the female vasculature is improved by TNF-α antagonism

Arenas, Ivan A.; Xu, Yi; Davidge, Sandra T.

doi:10.1152/ajpheart.00990.2005

Cited by 52 publications

(26 citation statements)

References 40 publications

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“…19,36,37 Recent studies also showed that in ovariectomized 12-to 15-month-old female Sprague-Dawley rats administration of etanercept (0.3 mg/kg, for 4 weeks) also improved endothelium-dependent vascular relaxations and decreased expression of the gp91 phox NAD(P)H oxidase subunits. 28,38 There are also studies showing that anti-TNF-␣ treatment with infliximab improves endothelial dysfunction in humans with vascular inflammation characterized by an up-regulation of TNF-␣. 23 We believe that these findings support the view that anti-TNF-␣ therapy, alone or in combination with standard treatments, may exert vasculoprotective effects in elderly humans.…”

Section: Discussionmentioning

confidence: 99%

Vasculoprotective Effects of Anti-Tumor Necrosis Factor-α Treatment in Aging

Csiszár

Labinskyy

Smith

et al. 2007

The American Journal of Pathology

192

169

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Vascular aging is associated with dysregulation of tumor necrosis factor (TNF)-␣ expression. TNF-␣ is a master regulator of vascular proatherogenic phenotypic changes, and it has been linked to endothelial dysfunction and apoptosis. To test the hypothesis that anti-TNF-␣ treatment exerts vasculoprotective effects in aging, aged (29 months old) F344 rats were treated with etanercept (1 mg/kg/week for 4 weeks), which binds and inactivates TNF-␣. In aged carotid arteries, relaxations to acetylcholine were decreased, and endothelial O 2. production was increased (as shown by dihydroethidine fluorescence measurements). Etanercept treatment significantly improved responses to acetylcholine and decreased vascular NAD(P)H oxidase activity and expression. In aged carotid and coronary arteries, there were increases in DNA fragmentation rate and caspase 3/7 activity (indicating an increased rate of apoptotic cell death), which were attenuated by etanercept treatment. In aged vessels, there was an up-regulation of inflammatory markers, including inducible nitric-oxide synthase and intercellular adhesion molecule-1, which was decreased by etanercept treatment. In carotid arteries of young animals, recombinant TNF-␣ elicited endothelial dysfunction, oxidative stress, and increased apoptosis and proinflammatory gene expression, mimicking many of the symptoms of vascular aging. Thus, we propose that anti-TNF-␣ treatment exerts anti-aging vasculoprotective effects.

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Section: Discussionmentioning

confidence: 99%

Vasculoprotective Effects of Anti-Tumor Necrosis Factor-α Treatment in Aging

Csiszár

Labinskyy

Smith

et al. 2007

The American Journal of Pathology

192

169

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“…These inflammatory factors include, tumor necrosis factor (TNF)-α, IL-6, and IL-1β, which are associated with increased risk of developing VCID (Zuliani et al, 2007). High levels of pro-inflammatory factors contribute to a pro-inflammatory microenvironment, which facilitates vascular dysfunction and promotes endothelial apoptosis, mainly through activation of NF-κB (Arenas et al, 2006; Donato et al, 2008; Donato et al, 2007; Ungvari et al, 2007; Zou et al, 2006). …”

Section: Cerebrovascular Biology and Agingmentioning

confidence: 99%

The impact of cerebrovascular aging on vascular cognitive impairment and dementia

Yang

Sun

et al. 2017

Ageing Research Reviews

157

128

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As human life expectancy rises, the aged population will increase. Aging is accompanied by changes in tissue structure, often resulting in functional decline. For example, aging within blood vessels contributes to a decrease in blood flow to important organs, potentially leading to organ atrophy and loss of function. In the central nervous system, cerebral vascular aging can lead to loss of the integrity of the blood-brain barrier, eventually resulting in cognitive and sensorimotor decline. One of the major of types of cognitive dysfunction due to chronic cerebral hypoperfusion is vascular cognitive impairment and dementia (VCID). In spite of recent progress in clinical and experimental VCID research, our understanding of vascular contributions to the pathogenesis of VCID is still very limited. In this review, we summarize recent findings on VCID, with a focus on vascular age-related pathologies and their contribution to the development of this condition.

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“…TNF-␣ has been shown to reduce NO bioavailability by decreasing eNOS expression or by increasing NO inactivation through stimulation of NADPH oxidase. Moreover, upregulation of TNF-␣ levels with aging is associated with a decrease in flow-mediated vasodilation leading to higher levels of shear stress (14).…”

Section: E Role Of No In the Phenotypic Adaptation Of Endothelial Cementioning

confidence: 99%

eNOS Activation by Physical Forces: From Short-Term Regulation of Contraction to Chronic Remodeling of Cardiovascular Tissues

Balligand¹,

Feron²,

Dessy³

2009

Physiological Reviews

397

328

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Nitric oxide production in response to flow-dependent shear forces applied on the surface of endothelial cells is a fundamental mechanism of regulation of vascular tone, peripheral resistance, and tissue perfusion. This implicates the concerted action of multiple upstream "mechanosensing" molecules reversibly assembled in signalosomes recruiting endothelial nitric oxide synthase (eNOS) in specific subcellular locales, e.g., plasmalemmal caveolae. Subsequent short- and long-term increases in activity and expression of eNOS translate this mechanical stimulus into enhanced NO production and bioactivity through a complex transcriptional and posttranslational regulation of the enzyme, including by shear-stress responsive transcription factors, oxidant stress-dependent regulation of transcript stability, eNOS regulatory phosphorylations, and protein-protein interactions. Notably, eNOS expressed in cardiac myocytes is amenable to a similar regulation in response to stretching of cardiac muscle cells and in part mediates the length-dependent increase in cardiac contraction force. In addition to short-term regulation of contractile tone, eNOS mediates key aspects of cardiac and vascular remodeling, e.g., by orchestrating the mobilization, recruitment, migration, and differentiation of cardiac and vascular progenitor cells, in part by regulating the stabilization and transcriptional activity of hypoxia inducible factor in normoxia and hypoxia. The continuum of the influence of eNOS in cardiovascular biology explains its growing implication in mechanosensitive aspects of integrated physiology, such as the control of blood pressure variability or the modulation of cardiac remodeling in situations of hemodynamic overload.

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Age-associated impairment in vasorelaxation to fluid shear stress in the female vasculature is improved by TNF-α antagonism

Cited by 52 publications

References 40 publications

Vasculoprotective Effects of Anti-Tumor Necrosis Factor-α Treatment in Aging

Vasculoprotective Effects of Anti-Tumor Necrosis Factor-α Treatment in Aging

The impact of cerebrovascular aging on vascular cognitive impairment and dementia

eNOS Activation by Physical Forces: From Short-Term Regulation of Contraction to Chronic Remodeling of Cardiovascular Tissues

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