Redirection of prostaglandin endoperoxide metabolism at the platelet-vascular interface in man.

Nowak, Jacek; FitzGerald, Garret A.

doi:10.1172/jci113895

Cited by 85 publications

(29 citation statements)

References 32 publications

(33 reference statements)

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“…A small skin incision (normal blood collection) induced a platelet vascular interface known to stimulate platelets to synthesize PGH 2 and consequently, TxA 2 as well as endothelial cells to generate PGH 2 and subsequently PGI 2 (Nowak and FitzGerald, 1989). These active eicosanoids were measured in blood leaving the wound site as TxB 2 and 6-keto-PGF 1␣ , respectively (Fig.…”

Section: In Vivo Transcellular Prostanoid Productionmentioning

confidence: 99%

Eicosanoid Transcellular Biosynthesis: From Cell-Cell Interactions to in Vivo Tissue Responses

Folco

Murphy²

2006

Pharmacol Rev

201

140

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Section: In Vivo Transcellular Prostanoid Productionmentioning

confidence: 99%

Eicosanoid Transcellular Biosynthesis: From Cell-Cell Interactions to in Vivo Tissue Responses

Folco

Murphy²

2006

Pharmacol Rev

201

140

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“…For example, restricted expression of thromboxane (Tx) synthase in platelets and restricted expression of PGI 2 synthase in endothelial cells account for the medical benefits of low-dose aspirin in thromboocclusive disorders (19). The distribution also accounts for the prothrombotic properties of platelets and the antithrombotic properties of the vascular endothelium (20,21). Restricted expression of 5-LO is also critical for the so-called transcellular biosynthesis of leukotrienes, in which an eicosanoid precursor generated by granulocytes or other cells can be enzymatically activated by platelets or endothelial cells (22)(23)(24).…”

Section: Restricted Expression Of Oxygenase and Isomerase Enzymesmentioning

confidence: 99%

Regulated formation of eicosanoids

Fitzpatrick

Soberman²

2001

J. Clin. Invest.

212

140

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“…This prostanoid is the principal metabolite of arachidonic acid produced by vascular endothelium and has potent vasodilator and platelet antiaggregatory effects (9). Under physiologic conditions, its circulating blood concentration is too low to exert a biologic effect, but platelet-inhibitory concentrations are formed at the site of vessel injury to limit the degree of platelet activation (21). Because PGlz formation in our patients was positively correlated to TxAz formation, it is possible that increased endothelial PGlz biosynthesis is a response of vascular endothelium to compensate for TxAz-mediated platelet activation and does not merely reflect damage to the endothelium.…”

Section: Discussionmentioning

confidence: 99%

Increased Biosynthesis of Vasoactive Prostanoids in Schönlein-Henoch Purpura

et al. 1992

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A8STRACT. Schonlein-Henoch purpura (SHP) is an acute immune-mediated vasculitis characterized by infiltration of polymorphonuclear leukocytes into the vessel wall causing damage to the vascular endothelium by the release of proteolytic enzymes. The local inflammatory and thrombotic process may be regulated by increased biosynthesis of vasoacti ve prostanoids. We investigated the biosynthesis of thromboxane A z (TxA z ), a potent vasoconstrictor and platelet agonist, prostacyclin (PGI z ), a vasodilator and platelet antagonist, and prostaglandin E z , a mediator of inflammation, in 14 children with SHP by physicochemical analysis of index metabolites in plasma and urine. TxA z and PGI2 biosynthesis in the systemic circulation was significantly elevated in the acute phase of the disease and correlated with the degree of clinical symptom s. Recurrent episodes of the disea se were associated with phasic increa ses of plasma and urinary TxA z and PGI z metabolites. Renal TxA 2 formation was highest in two patients presenting with the nephrotic syndrome and extracapillary glomerulonephritis. Pro staglandin E z biosynthesis in the systemic circulation was increased in the acute phase of the disea se. The enhanced TxAz formation is consistent with phasic platelet activation in SHP. The increased PGIz biosynthesis reflects endothelial cell damage and may be a response of vascular endothelium to modulate plateletvessel wall and leukocyte-vessel wall interactions. Increa sed prostaglandin E, formation, which probably derives from acti vated polymorphonuclear leukoc ytes and macrophages, is thought to be related to the inflammatory process in SHP. (Pediatr Res 32: 137-140, 1992 ) Abbreviations SHP, Schonlein-Henoch purpura SHP is the most com mon form of vasculitis in child ren (1). The vasculitis is initiated by the subendothelial deposition of IgA/IgG im m une complexes in small blood vessels (2). Complement activation induces infiltratio n of polym orph onuclear leukocytes, which by th e release of prot eolytic enzym es cause damage to th e vessel wall with secondary th rombosis and hem orrhage (3). Th e altered integrity of the vascular endothelium is likely to involve changes in prostanoid biosynthesis at the platelet vascular interface. Tx A 2 , the major cyclooxygenase product of ara chidonic acid in platelets, is a pot ent platelet aggregator and vasocon strictor (4). Th e potential pathophy siologic role of TxA 2 in acute immune-mediated vasculitic disorders has not yet been elucidated.In the present study, we investigated TxA z biosynthesis in childr en with SHP pros pectively during the disease process. To avoid sam pling and analytical probl em s, T xA z biosynthesis was examined by a highly specific and sensitive method, which measures two m ajor urinary enzymatic metabolites, I I-dehydroTx8 2 an d 2,3-dino r-TxB2, which are index metabolites of TxA 2 acti vatio n in th e systemic circulatio n (5, 6), and by measuri ng urin ary Tx B 2 , which predominantly reflects renal TxA 2 form ation (7). In addition , c...

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Redirection of prostaglandin endoperoxide metabolism at the platelet-vascular interface in man.

Cited by 85 publications

References 32 publications

Eicosanoid Transcellular Biosynthesis: From Cell-Cell Interactions to in Vivo Tissue Responses

Eicosanoid Transcellular Biosynthesis: From Cell-Cell Interactions to in Vivo Tissue Responses

Regulated formation of eicosanoids

Increased Biosynthesis of Vasoactive Prostanoids in Schönlein-Henoch Purpura

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