Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. Increased monolayer permeability and induction of procoagulant properties.

Ogawa, Satoshi; Gerlach, Herwig; Esposito, Ciro; Pasagian-Macaulay, Araxi; Brett, Jerold; Stern, David M.

doi:10.1172/jci114540

Cited by 300 publications

(117 citation statements)

References 55 publications

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“…This concept could reconcile the observation that hypoxia did not cause barrier disruption in the pulmonary vasculature (42) but disrupted aortic EC junctions (41). The contextual aspect of VE-PTP's role in stabilizing the endothelial barrier also needs to be considered in light of a recent study, which showed that inhibiting VE-PTP by a smallmolecule inhibitor stabilized the ocular vasculature in experimental models of retinal neovascularization (30).…”

Section: Methodsmentioning

confidence: 95%

“…Some studies have observed that hypoxia disrupted the endothelial barrier (41) and that VEGF, which is released in hypoxia, disassembled endothelial AJs by increasing VE-cadherin internalization (23). In contrast, rigorous in vivo studies in the sheep lung lymph fistula model performed by Bland and colleagues showed unequivocally that long-term hypoxia did not increase lung vascular permeability (42,43).…”

Section: Discussionmentioning

confidence: 99%

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HIF2α signaling inhibits adherens junctional disruption in acute lung injury

Gong¹,

Rehman²,

Tang³

et al. 2015

J. Clin. Invest.

112

124

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Section: Methodsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

HIF2α signaling inhibits adherens junctional disruption in acute lung injury

Gong¹,

Rehman²,

Tang³

et al. 2015

J. Clin. Invest.

112

124

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“…Human recombinant IGF-1 was purchased from Sigma. Hypoxia treatment was performed using an incubator attached to a hypoxia chamber (Coy Laboratory Products, Ann Arbor, MI) that maintained a humidified atmosphere with low oxygen tension (pO 2 ; 12-14 Torr) as described previously (20). In PI 3-kinase inhibition studies, the PI 3-kinase inhibitor wortmannin (Sigma) was added to the cultures 15 min before treatment with IGF-1.…”

Section: Methodsmentioning

confidence: 99%

Akt Activation Protects Hippocampal Neurons from Apoptosis by Inhibiting Transcriptional Activity of p53

Yamaguchi¹,

Tamatani²,

Matsuzaki³

et al. 2001

Journal of Biological Chemistry

219

142

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Survival factors suppress apoptosis by activating the serine/threonine kinase Akt. To investigate the molecular mechanism underlying activated Akt's ability to protect neurons from hypoxia or nitric oxide (NO) toxicity, we focused on the apoptosis-related functions of p53 and caspases. We eliminated p53 by employing p53-deficient neurons and increased p53 by infection with recombinant adenovirus capable of transducing p53 expression, and we now show that p53 is implicated in the apoptosis induced by hypoxia or NO treatments of primary cultured hippocampal neurons. Although hypoxia and NO induced p53, treatment with insulin-like growth factor-1 significantly inhibited caspase-3-like activation, neuronal death and transcriptional activity of p53. These insulin-like growth factor-1 effects are prevented by wortmannin, a phosphatidylinositol 3-kinase inhibitor. Adenovirus-mediated expression of activated-Akt kinase suppressed p53-dependent transcriptional activation of responsive genes such as Bax, suppressed caspase-3-like protease activity and suppressed neuronal cell death with no effect on the cellular accumulation and nuclear translocation of p53. In contrast, overexpression of kinase-defective Akt failed to suppress these same activities. These results suggest a mechanism where Akt kinase activation reduces p53's transcriptional activity that ultimately rescues neurons from hypoxia-or NO-mediated cell death.

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“…Furthermore, APC has distinct anti-inflammatory actions, and TM has mitogenic responses, that are separate from their antithrombotic functions, which modulate local response to inflammatory stimuli (39,40). Hypoxia downregulates TM transcription and expression of TM from cultured vascular endothelial cells (41). Further investigations are needed to both establish the mechanisms that lead to TM deficiency in the diabetic peripheral nerve microvasculature and determine whether TM-protein C antithrombotic mechanism impairments are linked to the development of diabetic neuropathy or its rate of progression.…”

Section: Diabetes Vol 51 June 2002mentioning

confidence: 99%

Thrombomodulin Deficiency in Human Diabetic Nerve Microvasculature

et al. 2002

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Human diabetic neuropathy is multifactorial in etiology, with ischemia as a final common pathology. Although impaired vascular endothelial cell function in diabetic microvascular injury is established, the role of thrombomodulin (TM)-dependent protein C antithrombotic mechanism in the pathogenesis of neuropathy is unclear. This neuropathologic case-control study investigated whether vascular endothelial TM expression is deficient in peripheral nerve microvessels in diabetic neuropathy. Sural nerve biopsies from 7 patients with diabetic neuropathy and 10 with axonal neuropathy without vasculopathy were immunostained with anti-TM and anti-von Willebrand factor (vWF; an endothelial cell marker) antibodies. The proportion of TM-positive microvessels was expressed relative to total vWF-staining vessels, according to vessel caliber and regional distribution within the nerve. In diabetic nerves compared with reference controls, the proportion of TMpositive endoneurial microvessels was 15-fold lower (0.02 vs. 0.30 in diabetic nerves vs. controls, P < 0.004), and the proportion of small-caliber epineurial microvessels was 10-fold lower (0.04 vs. 0.43, P < 0.001). No TM expression was detected at the perineurium in diabetic or control nerves. We demonstrate a substantial reduction of vascular endothelial TM expression throughout human diabetic neuropathy. These findings suggest that an impaired native TM-dependent protein C antithrombotic mechanism may contribute to microvascular ischemia in the pathogenesis of diabetic neuropathy.

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Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. Increased monolayer permeability and induction of procoagulant properties.

Cited by 300 publications

References 55 publications

HIF2α signaling inhibits adherens junctional disruption in acute lung injury

HIF2α signaling inhibits adherens junctional disruption in acute lung injury

Akt Activation Protects Hippocampal Neurons from Apoptosis by Inhibiting Transcriptional Activity of p53

Thrombomodulin Deficiency in Human Diabetic Nerve Microvasculature

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