Hypoxia-mediated induction of endothelial cell interleukin-1 alpha. An autocrine mechanism promoting expression of leukocyte adhesion molecules on the vessel surface.

Shreeniwas, Revati; Koga, Shin; Karakurum, Mehmet Çağrı; Pinsky, David J.; Kaiser, Eva; Brett, Jerold; Wolitzky, Barry A.; Norton, Christine R.; Plocinski, J; Benjamin, William R.

doi:10.1172/jci116122

Cited by 300 publications

(141 citation statements)

References 28 publications

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“…Indeed hypoxia exposure whether, in vitro or in vivo, is associated with rise in inflammatory markers. However, in the previous studies, as also quoted in the article by the authors, the duration of hypoxia exposure varied from 16 to 72 h [2][3][4][5] On the contrary, in the present study duration of simulated hypoxia of 4500 m was only 30 min. It remains obscure that those changes seen in the chemokines are actually the result of hypoxia induced inflammation or otherwise.…”

Section: To the Editorcontrasting

confidence: 51%

Chemokines in High Altitude Pulmonary Edema

Bhattachar

Sikri

2016

Ind J Clin Biochem

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Section: To the Editorcontrasting

confidence: 51%

Chemokines in High Altitude Pulmonary Edema

Bhattachar

Sikri

2016

Ind J Clin Biochem

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“…Our hypothesis of local muscle tissue hypoxia is supported by increased expression of interleukin-1␣ (IL-1␣), IL-1␤, transforming growth factor ␤, intercellular adhesion molecule 1, and vascular cellular adhesion molecule 1 in the muscle tissue of patients with myositis (10)(11)(12)(13)(14), because these molecules are known to be up-regulated by hypoxia (10)(11)(12)(13). Moreover, the endothelial cells are frequently thickened, resembling endothelial cells of high endothelium venules (HEV), indicating their activation (3,10,11,(15)(16)(17). Notably, such phenotypically changed endothelial cells were observed in patient muscle tissue irrespective of inflammation (15).…”

Section: Polymyositis (Pm) and Dermatomyositis (Dm)mentioning

confidence: 92%

Vascular endothelial growth factor is highly expressed in muscle tissue of patients with polymyositis and patients with dermatomyositis

Grundtman¹,

Tham²,

Ulfgren³

et al. 2008

Arthritis & Rheumatism

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Objective. To investigate the expression of vascular endothelial growth factor (VEGF) in muscle biopsy specimens and serum from patients with polymyositis and patients with dermatomyositis compared with that in healthy control subjects.Methods. Muscle biopsy specimens from 33 patients with polymyositis or dermatomyositis and 15 healthy control subjects and serum samples from 56 patients and 56 healthy control subjects were analyzed. Patients were categorized into 3 groups, depending on disease duration and the presence or absence of inflammatory infiltrates. The expression of VEGF and the vessel marker CD31 in muscle was analyzed by immunohistochemistry, the expression of VEGF messenger RNA (mRNA) was analyzed by in situ hybridization, and serum levels of VEGF were determined by enzymelinked immunosorbent assay.Results. Patients with polymyositis or dermatomyositis in the early or chronic phase without inflammatory infiltrates had a decreased total number of capillaries compared with healthy individuals. In patients with early disease without inflammatory infil-

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“…One possibility was that polymorphonuclear leukocytes (PMN) became adherent to the hypoxemic vessel wall due to translocation of P-selectin to the cell surface 15 or cytokine-mediated upregulation of intercellular adhesion molecule-1 expression. 19 Subsequent leukocyte activation could generate reactive oxygen intermediates, damaging the vessel wall and causing exposure of tissue factor in subendothelial layers of the vessel wall. However, antibody-induced depletion of PMNs had no effect on fibrin accumulation.…”

Section: Hypoxia-associated Expression Of Tissue Factormentioning

confidence: 99%

Hypoxia/Hypoxemia-Induced Activation of the Procoagulant Pathways and the Pathogenesis of Ischemia-Associated Thrombosis

Yan

Mackman

Kisiel

et al. 1999

ATVB

172

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Abstract-Although oxygen deprivation has long been associated with triggering of the procoagulant pathway and venous thrombosis, blood hypoxemia and stasis by themselves do not lead to fibrin formation. A pathway is outlined through which diminished levels of oxygen activate the transcription factor early growth response-1 (Egr-1) leading to de novo transcription/translation of tissue factor in mononuclear phagocytes and smooth muscle cells, which eventuates in vascular fibrin deposition. The procoagulant response is magnified by concomitant suppression of fibrinolysis by hypoxia-mediated upregulation of plasminogen activator inhibitor-1. These data add a new facet to the biology of thrombosis associated with hypoxemia/stasis and imply that interference with mechanisms causing Egr-1 activation in response to oxygen deprivation might prevent vascular fibrin deposition occurring in ischemia without directly interfering with other pro/anticoagulant pathways. Key Words: tissue factor Ⅲ hypoxia Ⅲ ischemia Ⅲ Egr-1 Ⅲ PAI-1 I n the 1850s, Virchow described the association between venous thrombosis and a triad of contributing factors, including hypercoagulability, vascular damage, and vascular stasis. 1 More recently, venous stasis has been linked to the rapid decline in intravascular oxygen tension and thrombus formation in veins of the lower extremities. [2][3][4] Definition of mechanisms through which low levels of oxygen cause blood to clot has been more elusive. The Wessler stasis model of venous thrombosis, 5,6 in which a rabbit vascular segment (typically the jugular vein) is occluded and a fibrin clot subsequently forms after addition of a procoagulant, demonstrated that acute lack of blood flow and/or hypoxemia, although necessary, were not sufficient, at least acutely, to trigger clot formation. Without inclusion of a strong procoagulant stimulus, such as activated clotting factors (eg, Factors IXa, Xa, or thrombin), fibrin deposition did not occur. These observations have been extended to different types of vessels, and this has led to the same conclusion; acute occlusion of normal vessels with their normal blood content does not by itself promote fibrin formation. This situation must be differentiated from that of an atherosclerotic or other pathologic vessel, in which abundant neointimal tissue factor, a maximal prothrombotic stimulus, is immediately exposed to blood contents, triggering rapid coagulation. In fact, the intact, healthy vessel wall has very low levels of tissue factor with an increasing gradient toward the adventitia. The cell type most uniformly accepted as being capable of expressing substantive amounts of tissue factor within the intravascular space in response to environmental stimuli is the mononuclear phagocyte, although polymorphonuclear leukocytes may also contribute, and endothelial cells have been shown to produce tissue factor in selected settings. 7,8 Thus it may not be surprising that a brief period of hypoxemia and/or stasis alone in a normal vessel are not sufficient to trigger ...

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Hypoxia-mediated induction of endothelial cell interleukin-1 alpha. An autocrine mechanism promoting expression of leukocyte adhesion molecules on the vessel surface.

Cited by 300 publications

References 28 publications

Chemokines in High Altitude Pulmonary Edema

Chemokines in High Altitude Pulmonary Edema

Vascular endothelial growth factor is highly expressed in muscle tissue of patients with polymyositis and patients with dermatomyositis

Hypoxia/Hypoxemia-Induced Activation of the Procoagulant Pathways and the Pathogenesis of Ischemia-Associated Thrombosis

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