Cyclooxygenases-1 and −2 of Endothelial Cells Utilize Exogenous or Endogenous Arachidonic Acid for Transcellular Production of Thromboxane

Karim, Souad; Habib, Aı̈da; Lévy-Toledano, S; Maclouf, Jacques

doi:10.1074/jbc.271.20.12042

Cited by 120 publications

(81 citation statements)

References 35 publications

(36 reference statements)

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“…Aspirin, an irreversible cyclooxygenase inhibitor, lacked an antiangiogenic effect. This absence of activity may be related to the observation that the irreversible inhibition of cyclooxygenase synthetases by aspirin resulted in a compensatory production of COX-2 with bioactivity (Karim et al, 1995). Still, we cannot rule out that some differences in antiangiogenic activity of the NSAIDs were caused by a difference in pharmacokinetics.…”

Section: Discussionmentioning

confidence: 82%

Combination oral antiangiogenic therapy with thalidomide and sulindac inhibits tumour growth in rabbits

et al. 1998

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Neovascularization facilitates tumour growth and metastasis formation. In our laboratory, we attempt to identify clinically available oral efficacious drugs for antiangiogenic activity. Here, we report which non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit corneal neovascularization, induced by basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF). This antiangiogenic activity may contribute to the known effects of NSAIDs on gastric ulcers, polyps and tumours. We found that sulindac was one of the most potent antiangiogenic NSAIDs, inhibiting bFGF-induced neovascularization by 50% and VEGF-induced neovascularization by 55%. Previously, we reported that thalidomide inhibited growth factor-induced corneal neovascularization. When we combined sulindac with thalidomide, we found a significantly increased inhibition of bFGF- or VEGF-induced corneal neovascularization (by 63% or 74% respectively) compared with either agent alone ( P < 0.01). Because of this strong antiangiogenic effect, we tested the oral combination of thalidomide and sulindac for its ability to inhibit the growth of V2 carcinoma in rabbits. Oral treatment of thalidomide or sulindac alone inhibited tumour growth by 55% and 35% respectively. When given together, the growth of the V2 carcinoma was inhibited by 75%. Our results indicated that oral antiangiogenic combination therapy with thalidomide and sulindac may be a useful non-toxic treatment for cancer. © 1999 Cancer Research Campaign

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Section: Discussionmentioning

confidence: 82%

Combination oral antiangiogenic therapy with thalidomide and sulindac inhibits tumour growth in rabbits

et al. 1998

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“…Although COX-1 was originally described as the constitutive isoform expressed in most cell types, 4 COX-1 can be induced in specific cells by several stimuli such as PGE 2 , arachidonic acid, and VEGF. 37,38 According to our results, the links between PGs and CT-1 appear to be bidirectional: COX-2 inhibitors block CT-1 expression after PH and, conversely, therapy with AdCT-1 to NS-398 -treated rats induces PGs. The interactions between PGs and CT-1 are supported by our in vitro observations.…”

Section: Discussionmentioning

confidence: 99%

Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration

et al. 2005

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Prostaglandins are hepatoprotective molecules generated in liver regeneration by the rapid induction of cyclooxygenase-2 (COX-2). Cardiotrophin-1 (CT-1) and vascular endothelial growth factor (VEGF) are other hepatoprotective mediators upregulated at 24 hours after partial hepatectomy. The interactions among these molecules during liver regeneration have not yet been defined. Here we show that rats subjected to partial hepatectomy treated with NS-398, a specific COX-2 inhibitor, exhibited cell cycle arrest, increased hepatocyte apoptosis, persistent extracellular signal-regulated kinase (ERK) 1/2 activation, and increased interleukin-6 production. These changes were associated with downregulation of CT-1 and COX-1 and altered pattern of VEGF expression. Administration of an adenovirus encoding CT-1 to NS-398-treated rats restituted normal levels of COX-1, prostaglandins, and VEGF in the liver after partial hepatectomy and restored normal liver regeneration. Furthermore, the stimulation of isolated rat hepatocytes with CT-1 increased COX-1, COX-2, and VEGF messenger RNAs and prostaglandin synthesis. Conversely, the addition of prostaglandin E1 to the culture increased CT-1 and VEGF production. In conclusion, COX-2 activation and production of prostaglandins soon after partial hepatectomy are essential requirements for hepatocyte proliferation and for the correct induction of both CT-1 and VEGF. CT-1 can restore liver regeneration after COX-2 inhibition by increasing VEGF, COX-1 expression, and prostaglandin synthesis. (HEPATOLOGY 2005;41:460-469.)

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“…Appreciation of the importance of cell-cell interactions in the vasculature as well as transcellular metabolism as critical facets of thrombosis and inflammation is now widely recognized (Marcus et al, 1982;Karim et al, 1996;Marcus, 1999). These phenomena are pertinent with regard to platelets, leukocytes, erythrocytes, and endothelial cells.…”

Section: Ecto-adpase/cd39 (Ntpdase-1) the Major Inhibitor Of Platelementioning

confidence: 99%

Metabolic Control of Excessive Extracellular Nucleotide Accumulation by CD39/Ecto-Nucleotidase-1: Implications for Ischemic Vascular Diseases

Marcus

Broekman

Drosopoulos

et al. 2003

J Pharmacol Exp Ther

120

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Platelets are responsible for maintaining vascular integrity. In thrombocytopenic states, vascular permeability and fragility increase, presumably due to the absence of this platelet function. Chemical or physical injury to a blood vessel induces platelet activation and platelet recruitment. This is beneficial for the arrest of bleeding (hemostasis), but when an atherosclerotic plaque is ulcerated or fissured, it becomes an agonist for vascular occlusion (thrombosis). Experiments in the late 1980s cumulatively indicated that endothelial cell CD39 -an ecto-ADPase-reduced platelet reactivity to most agonists, even in the absence of prostacyclin or nitric oxide. As discussed herein, CD39 rapidly and preferentially metabolizes ATP and ADP released from activated platelets to AMP, thereby drastically reducing or even abolishing platelet aggregation and recruitment. Since ADP is the final common agonist for platelet recruitment and thrombus formation, this finding highlights the significance of CD39. A recombinant, soluble form of human CD39, solCD39, has enzymatic and biological properties identical to the full-length form of the molecule and strongly inhibits human platelet aggregation induced by ADP, collagen, arachidonate, or TRAP (thrombin receptor agonist peptide). In sympathetic nerve endings isolated from guinea pig hearts, where neuronal ATP enhances norepinephrine exocytosis, solCD39 markedly attenuated norepinephrine release. This suggests that NTPDase (nucleoside triphosphate diphosphohydrolase) could exert a cardioprotective action by reducing ATP-mediated norepinephrine release, thereby offering a novel therapeutic approach to myocardial ischemia and its consequences. In a murine model of stroke, driven by excessive platelet recruitment, solCD39 reduced the sequelae of stroke, without an increase in intracerebral hemorrhage. CD39 null mice, generated by deletion of apyrase-conserved regions 2 to 4, exhibited a decrease in postischemic perfusion and an increase in cerebral infarct volume when compared with controls. "Reconstitution" of CD39 null mice with solCD39 reversed these changes. We hypothesize that solCD39 has potential as a novel therapeutic agent for thrombotic diatheses. The Hemostatic MechanismThe hemostatic process consists of a series of physiologic and biochemical reactions that culminate in the arrest of bleeding from blood vessels that have been severed or traumatized physically or chemically. Hemostasis is accomplished via the interaction of three biological systems: 1) components of the vasculature per se, including endothelial cells; 2) blood platelets; and 3) plasma proteins comprising the intrinsic and extrinsic coagulation pathways (Marcus, 1999). Qualitative or quantitative deficiencies in any one of these systems result in a defect of hemostasis, coagulation, or both. These abnormalities can lead to a hemorrhagic diathesis that is clinically mild, moderate, or severe. -methyladenosine-3Ј,5Ј-diphosphate; NTPDase, nucleoside triphosphate diphosphohydrolase.

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Cyclooxygenases-1 and −2 of Endothelial Cells Utilize Exogenous or Endogenous Arachidonic Acid for Transcellular Production of Thromboxane

Cited by 120 publications

References 35 publications

Combination oral antiangiogenic therapy with thalidomide and sulindac inhibits tumour growth in rabbits

Combination oral antiangiogenic therapy with thalidomide and sulindac inhibits tumour growth in rabbits

Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration

Metabolic Control of Excessive Extracellular Nucleotide Accumulation by CD39/Ecto-Nucleotidase-1: Implications for Ischemic Vascular Diseases

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