Prostaglandin I2 is not a major metabolite of arachidonic acid in cultured endothelial cells from human foreskin microvessels.

Charo, Israel F.; Shak, Steven; Karasek, Marvin A.; Davison, Pamela; Goldstein, Ira M.

doi:10.1172/jci111509

Cited by 138 publications

(39 citation statements)

References 20 publications

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“…We also demonstrated that bradykinin-stimulated 13,14-dihydro-15-oxo-PGF2,, exhibits a similar time course of inhibition and recovery following aspirin to that of bradykinin-stimulated 6-oxo-PGF1*. It is likely that this metabolite reflects PGE2 production by microvascular endothelium (Charo et al, 1984;Barrow etal., 1987;Ritter et al, 1987a), suggesting that endothelial cyclo-oxygenase turns over rapidly in man. In contrast to our findings, Hamberg (1972) found that sodium salicylate, 750 mg four times daily for 3 days, substantially inhibited excretion of a urinary metabolite of E-series prostaglandins under basal conditions.…”

Section: Discussionsupporting

confidence: 53%

Differential effect of aspirin on thromboxane and prostaglandin biosynthesis in man.

Ritter

Cockcroft

Doktor

et al. 1989

Brit J Clinical Pharma

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1 Effects of a single intravenous dose of aspirin (600 mg) on bradykinin-stimulated prostaglandin (PG) and on thromboxane (TX) biosynthesis were determined in nine healthy male volunteers. Plasma concentrations of 6-oxo-PGF,1ll and 13,14-dihydro-15-oxo-PGF2a were measured in samples obtained during repeated 10 min intravenous infusions of bradykinin before and up to 6 h after the dose of aspirin. TXB2 was measured in serum from blood allowed to clot at 370 C. 2 Aspirin inhibited bradykinin stimulated PG and platelet TX biosynthesis 0.5 h after the dose. Serum TXB2 remained low, whereas PG synthesis recovered within 6 h. 3 Effects of intravenous sodium salicylate (600 mg) were studied identically in eight subjects. Prostanoid biosynthesis was not inhibited. 4 Biosynthesis of prostacyclin and TXA2 under basal conditions was studied in eight subjects by measuring 2,3-dinor-6-oxo-PGF1,, and 2,3-dinor-TXB2 in hourly urine samples obtained during and after intravenous infusion of aspirin and, on a separate occasion, of vehicle.5 Aspirin infusion reduced urinary excretion of both metabolites > 90%, but excretion of 2,3-dinor-6-oxo-PGF1a recovered more rapidly than did that of 2,3-dinor-TXB2. 6 We conclude that cyclo-oxygenase is rapidly synthesised in bradykinin-responsive tissues in vivo and that this reflects similarly rapid enzyme biosynthesis in tissues that produce PGI2 under basal conditions. Keywords thromboxane A2 prostacyclin prostaglandin metabolites bradykinin aspirin

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Section: Discussionsupporting

confidence: 53%

Differential effect of aspirin on thromboxane and prostaglandin biosynthesis in man.

Ritter

Cockcroft

Doktor

et al. 1989

Brit J Clinical Pharma

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“…The heterogeneity of microvascular endothelial cells (MECs) derived from different organs [1][2][3][4][5][6] indicates strongly that these cells have specialised functions at different anatomical sites. Thus by studying the features of tissue-derived endothelium, we might gain considerable insight into the physiological and pathological processes taking place within a specific organ.…”

Section: Introductionmentioning

confidence: 99%

Expression of nephrin by human pancreatic islet endothelial cells

et al. 2005

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Aims/hypothesis: The islet microcirculation has morphological characteristics resembling those of renal glomeruli. Transcription of the nephrin gene, a highly specific barrier protein of the slit diaphragm of podocyte foot processes, has been reported in the pancreas, although its cellular localisation and function remain to be defined. In this study, we purified and characterised microvascular endothelial cells (MECs) isolated from human islets and investigated the expression and distribution of nephrin on these cells. Methods: Human islet MECs were extracted and purified using anti-CD105-coated immunomagnetic beads and their endothelial characteristics were confirmed by expression of classical endothelial markers and basal high-level expression of intercellular adhesion molecule-1 and TNF-α-inducible vascular cell adhesion molecule-1. Nephrin expression was assessed by immunofluorescence, flow cytometric analysis and western blotting on cell lysates, as well as by RT-PCR. Results: Immunofluorescence studies detected nephrin in a fine, punctate, diffuse pattern on cultured islet MECs, and also in human pancreatic islet sections. In both cases nephrin colocalised with endothelial markers. TNF-α treatment induced a marked reduction and redistribution of the protein in one or multiple aggregates. Nephrin expression was confirmed by flow cytometry, western blotting and RT-PCR studies. In contrast, nephrin could not be detected at the protein or mRNA level in human macro-and microvascular cells from other sites. Conclusions/interpretation: Nephrin is expressed at protein and mRNA levels in islet microendothelium, supporting the hypothesis that islet MECs exhibit distinctive morphological characteristics that indicate functional specialisation of potential pathophysiological importance.

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“…A deeper knowledge of tissue-derived endothelium might help us understand its physiological properties and the pathological processes occurring within a specific organ. It is, in fact, widely accepted that phenotype and function of microvascular endothelial cells (MECs) derived from different vascular beds are heterogeneous [3][4][5][6][7][8], supporting the proposal that tissue-specific vascular beds have specialised functions.…”

Section: Introductionmentioning

confidence: 99%

“…Most of our knowledge on the active participation of endothelial cells in physiopathological processes derives from studies on endothelial cells derived from umbilical vein, which are easily isolated and cultured [26]. However, it is conceivable that these large-vessel endothelial cells do not exhibit the phenotypic and functional characteristics of the relevant microvasculature [3][4][5][6][7][8]27]. Studies on the biology of microvascular endothelial cells are hampered by difficulties in isolating and culturing large numbers of pure cells from any organ, and by their limited life span.…”

Section: Introductionmentioning

confidence: 99%

Primary and immortalised human pancreatic islet endothelial cells: phenotypic and immunological characterisation

et al. 2005

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Aims/hypothesis: Studies on the biology of the microvascular endothelial cells (MECs) that surround and penetrate the pancreatic islets are hampered by difficulties in isolating and culturing large numbers of pure cells. We aimed to morphologically and functionally characterise primary MECs purified and cultured from human islets, and to establish a simian virus 40 (SV40)-immortalised cell line from these primary cultures. Materials and methods: Human islet MECs were extracted and purified using anti-CD105 coated immunomagnetic beads, and endothelial markers and surface molecules analysed by flow cytometric analysis. An immortalised cell line was then established by using a chimeric adeno5/SV40 virus. Results: Islet MECs expressed classic and specific endothelial markers, a high basal level of intercellular adhesion molecule-1, and low levels of E-selectin and TNF (previously known as TNF-α) inducible vascular cell adhesion molecule-1. IFNG (previously known as IFN-γ) induced expression of HLA class II molecules. The immortalised islet MECs expanded rapidly, exhibited increased DNA synthesis, and were passaged approximately 30 times, without signs of senescence. They retained the endothelial characteristics of the parental cells, and behaved as the primary cells in terms of TNF stimulation of expression of adhesion molecules and support of leucocyte adhesion and transmigration. Conclusions/interpretation: The immortalised islet MECs that we have established could effectively represent a substitute for primary counterparts for in vitro studies on the role of the microvasculature in pathophysiological processes involved in type 1 and type 2 diabetes.

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Prostaglandin I2 is not a major metabolite of arachidonic acid in cultured endothelial cells from human foreskin microvessels.

Cited by 138 publications

References 20 publications

Differential effect of aspirin on thromboxane and prostaglandin biosynthesis in man.

Differential effect of aspirin on thromboxane and prostaglandin biosynthesis in man.

Expression of nephrin by human pancreatic islet endothelial cells

Primary and immortalised human pancreatic islet endothelial cells: phenotypic and immunological characterisation

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