Rate of Vasoconstrictor Prostanoids Released by Endothelial Cells Depends on Cyclooxygenase-2 Expression and Prostaglandin I Synthase Activity

Camacho, Mercedes; López-Belmonte, Jesús; Vilá, Luis M.

doi:10.1161/01.res.83.4.353

Cited by 140 publications

(127 citation statements)

References 59 publications

(33 reference statements)

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“…Such data suggest that NO may regulate the COX pathway in human pulmonary arteries as has been reported for other vascular endothelium (Salvemini et al, 1996;Davidge, 2001). The observation that NO or OONO À may inhibit prostacyclin synthase (PGIS) and the release of PGI 2 has also been shown in human saphenous veins (Barker et al, 1996), HUVEC (Camacho et al, 1998), bovine endothelial cells (Doni et al, 1988) and aortic preparations (Zou & Ullrich, 1996). Since NO production appears more pronounced in human pulmonary veins when compared with the arteries, this kind of PGIS-control may explain in part the reduced production of PGI 2 by the veins.…”

Section: Norel Et Alsupporting

confidence: 54%

Prostacyclin release and receptor activation: differential control of human pulmonary venous and arterial tone

Norel

Walch

Gascard

et al. 2004

British J Pharmacology

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1 In human pulmonary vascular preparations, precontracted arteries were more sensitive to the relaxant effect of acetylcholine (ACh) than veins (pD 2 values: 7.2570.08 (n ¼ 23) and 5.9270.09 (n ¼ 25), respectively). Therefore, the role of prostacyclin (PGI 2 ) was explored to examine whether this mediator may be responsible for the difference in relaxation. 2 In the presence of the cyclooxygenase (COX) inhibitor, indomethacin (INDO), the ACh relaxations were reduced in arteries but not in veins. On the contrary, an inhibitor (L-NOARG) of the nitric oxide synthase blocked preferentially the relaxation in veins. 3 A greater release of 6-keto-PGF 1a , the stable metabolite of PGI 2 , was observed in arterial preparations than in venous preparations when stimulated with either ACh or arachidonic acid (AA). 4 Exogenous PGI 2 produced a reduced relaxant effect in the precontracted vein when compared with the artery. In the presence of the EP 1 -receptor antagonist AH6809, the PGI 2 relaxation of veins was similar to arteries. 5 In veins, AA (0.1 mM) produced a biphasic response, namely, a contraction peak (0.4-0.5 g) followed by a relaxation. These contractions in venous preparations were abolished either in the absence of endothelium or in the presence of INDO or an EP 1 -receptor antagonist (AH6809, SC19220). In the arterial preparations AA induced only relaxations. 6 In both vascular preparations, COX-1 but not the COX-2 protein was detected in microsomal preparations derived from homogenized tissues or freshly isolated endothelial cells. 7 The differential vasorelaxations induced by ACh may be explained, in part, by a more pronounced production and release of PGI 2 in human pulmonary arteries than in the veins. In addition, while PGI 2 induced relaxation by activation of IP-receptors in both types of vessels, a PGI 2 constrictor effect was responsible for masking the relaxation in the veins by activation of the EP 1 -receptor.

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Section: Norel Et Alsupporting

confidence: 54%

Prostacyclin release and receptor activation: differential control of human pulmonary venous and arterial tone

Norel

Walch

Gascard

et al. 2004

British J Pharmacology

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“…It is intriguing that, despite the coexistence of both COX-1 and COX-2 in HCAEC, histamine is able to segregate its influence on COX-2/PGE 2 /PGI 2 pathway and not on COX-1/TXA 2 pathway. It is also of interest that the increase in the production of prostanoids is not always associated with parallel induction of the expression or activity of a distinct PG synthase (27). Because a physiological balance in the production of PGI 2 and TXA 2 by endothelial cells is critical for the maintenance of vascular integrity and control of thrombosis (28,29), the histamine-induced shift of prostanoid equilibrium in favor of PGI 2 production is noteworthy and supports its well-recognized vasodilatory and vasoprotective function.…”

Section: Figurementioning

confidence: 99%

Histamine Directly and Synergistically with Lipopolysaccharide Stimulates Cyclooxygenase-2 Expression and Prostaglandin I2 and E2 Production in Human Coronary Artery Endothelial Cells

Tan

Essengue

Talreja

et al. 2007

The Journal of Immunology

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Although histamine plays an essential role in inflammation, its influence on cyclooxygenases (COX) and prostanoid homeostasis is not well understood. In this study, we investigated the effects of histamine on the expression of COX-1 and COX-2 and determined their contribution to the production of PGE2, prostacyclin (PGI2), and thromboxane A2 in human coronary artery endothelial cells (HCAEC). Incubation of HCAEC monolayers with histamine resulted in marked increases in the expression of COX-2 and production of PGI2 and PGE2 with no significant change in the expression of COX-1. Histamine-induced increases in PGI2 and PGE2 production were due to increased expression and function of COX-2 because gene silencing by small interfering RNA or inhibition of the catalytic activity by a COX-2 inhibitor blocked prostanoid production. The effects of histamine on COX-2 expression and prostanoid production were mediated through H1 receptors. In addition to the direct effect, histamine was found to amplify LPS-stimulated COX-2 expression and PGE2 and PGI2 production. In contrast, histamine did not stimulate thromboxane A2 production in resting or LPS-activated HCAEC. Histamine-induced increases in the production of PGE2 and PGI2 were associated with increased expression of mRNA encoding PGE2 and PGI2 synthases. The physiological role of histamine on the regulation of COX-2 expression in the vasculature is indicated by the findings that the expression of COX-2 mRNA, but not COX-1 mRNA, was markedly reduced in the aortic tissues of histidine decarboxylase null mice. Thus, histamine plays an important role in the regulation of COX-2 expression and prostanoid homeostasis in vascular endothelium.

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“…However, the endothelium has been reported to synthesize TXA 2 in addition to PGI 2 (6), and both COX isoforms have been observed, with only COX-1 being detectable in unstimulated cells (6,7). Endothelial COX-2 can be up-regulated in vitro by inflammatory stimuli (6,8) and shear stress (7,9). Because the balance between PGI 2 and TXA 2 production is central in the maintenance of vascular tone and platelet aggregation, determination of the roles of endothelial COX isozymes, particularly with regard to the contribution of COX-2 in the regulation of prostanoid biosynthesis by the endothelium, is important.…”

Section: T He Prostanoids Prostacyclin (Pgi 2 )mentioning

confidence: 99%

Roles of Cyclooxygenase (COX)-1 and COX-2 in Prostanoid Production by Human Endothelial Cells: Selective Up-Regulation of Prostacyclin Synthesis by COX-2

Caughey

Cleland

Penglis

et al. 2001

The Journal of Immunology

247

183

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The two cyclooxygenase (COX) isoforms, COX-1 and COX-2, both metabolize arachidonic acid to PGH2, the common substrate for thromboxane A2 (TXA2), prostacyclin (PGI2), and PGE2 synthesis. We characterized the synthesis of these prostanoids in HUVECs in relation to COX-1 and COX-2 activity. Untreated HUVEC expressed only COX-1, whereas addition of IL-1β caused induction of COX-2. TXA2 was the predominant COX-1-derived product, and TXA2 synthesis changed little with up-regulation of COX-2 by IL-1β (2-fold increase). By contrast, COX-2 up-regulation was associated with large increases in the synthesis of PGI2 and PGE2 (54- and 84-fold increases, respectively). Addition of the selective COX-2 inhibitor, NS-398, almost completely abolished PGI2 and PGE2 synthesis, but had little effect on TXA2 synthesis. The up-regulation of COX-2 by IL-1β was accompanied by specific up-regulation of PGI synthase and PGE synthase, but not TX synthase. An examination of the substrate concentration dependencies showed that the pathway of TXA2 synthesis was saturated at a 20-fold lower arachidonic acid concentration than that for PGI2 and PGE2 synthesis. In conclusion, endothelial prostanoid synthesis appears to be differentially regulated by the induction of COX-2. The apparent PGI2 and PGE2 linkage with COX-2 activity may be explained by a temporal increase in total COX activity, together with selective up-regulation of PGI synthase and PGE synthase, and different kinetic characteristics of the terminal synthases. These findings have particular importance with regard to the potential for cardiovascular consequences of COX-2 inhibition.

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Rate of Vasoconstrictor Prostanoids Released by Endothelial Cells Depends on Cyclooxygenase-2 Expression and Prostaglandin I Synthase Activity

Cited by 140 publications

References 59 publications

Prostacyclin release and receptor activation: differential control of human pulmonary venous and arterial tone

Prostacyclin release and receptor activation: differential control of human pulmonary venous and arterial tone

Histamine Directly and Synergistically with Lipopolysaccharide Stimulates Cyclooxygenase-2 Expression and Prostaglandin I2 and E2 Production in Human Coronary Artery Endothelial Cells

Roles of Cyclooxygenase (COX)-1 and COX-2 in Prostanoid Production by Human Endothelial Cells: Selective Up-Regulation of Prostacyclin Synthesis by COX-2

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