Recovery of prostacyclin production by de-endothelialized rabbit aorta. Critical role of neointimal smooth muscle cells.

Eldor, Amiram; Falcone, Domenick J.; Hajjar, David P.; Minick, C R; Weksler, BB

doi:10.1172/jci110090

Cited by 166 publications

(50 citation statements)

References 30 publications

(30 reference statements)

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“…3 Because PGI 2 formed by the deeper layers of the media normally does not reach the luminal surface, endothelial tissue is responsible for nearly all PGI 2 at this critical interface of platelet-vessel wall interaction. 4 The usual source of substrate for PGI 2 production appears to be intracellular pools of esterified fatty acid within the endothelium; upon synthesis, it is released immediately from the cells, so that synthesis is synonymous with release. 48 Skidgel and Printz 36 reported that rat arteries generated greater quantities of PGI 2 than did veins and further postulated a segmental distribution of PGI 2 synthetase activity in blood vessels.…”

Section: Resultsmentioning

confidence: 99%

Regional variability of prostacyclin biosynthesis.

et al. 1989

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To Investigate the regional variability In arterial and venous endothellal prostacyclin (PGIj) biosynthesis, we obtained 1-cm segments of carotid arteries, external jugular veins, femoral arteries and veins, lilac arteries and veins, Inferior venae cavae (IVC), and aortas from 17 dogs. Vessel lumlnal PGI 2 production was measured In the basal state by radlolmmunoassay of 6-keto-prostaglandln F 1o (6-keto-PGF 1a ). A total of 90 arterial specimens (57, 19, and 14 segments, respectively, of femoral/carotid arteries, lilac arteries, and aorta) and 41 venous specimens (15,10, and 16 segments, respectively, of femoral/jugular veins, lilac veins, and IVC) were analyzed. Overall, arterial endothellal 6-keto-PGF 1a was higher than venous (8.1 ±0.5 ng/ml vs. 4.9±0.7 ng/ml, p<0.0004); 6-keto-PGF 1a levels were greater In the arteries than In their corresponding veins [femoral/carotid arteries (6.3±0.4 ng/ml) vs. femoral/jugular vein (2.1 ±0.4 ng/ml), /xO.0002; Iliac arteries (9.3±1.0 ng/ml) vs. iliac veins (4.8±0.9 ng/ml), /xO.005; aorta (14.0±1.6 ng/ml) vs. IVC (

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Section: Resultsmentioning

confidence: 99%

Regional variability of prostacyclin biosynthesis.

et al. 1989

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“…The chamber excludes cut tissue edges from study and has previously been shown to measure release of PGI2 released from endothelium rather than from smooth muscle layers of the vessel wall. 26 The chambers were designed and made available by Dr. Eric Grabowski.…”

Section: Methodsmentioning

confidence: 99%

Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

Weksler¹,

Tack-Goldman²,

Subramanian³

et al. 1985

Circulation

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The relationship between the antithrombotic and antiplatelet effects of aspirin is complex, since aspirin influences other systems that protect against thrombosis as well as inhibiting platelet function. We investigated possible cumulative effects of low-dose aspirin on vascular production of prostacyclin in patients with documented atherosclerotic cardiovascular disease. Candidates for coronary artery vein graft bypass ingested 20 mg of aspirin daily during the week before surgery, and platelet aggregation, platelet formation of thromboxane A2 (TXA2), aortic and saphenous vein production of prostacyclin (PGI2), and hemostatic status were measured at the time of the bypass surgery. Low-dose aspirin markedly inhibited platelet aggregation responses and reduced TXA2 generation by greater than 90%, effects similar to those observed with much higher doses of aspirin. Both aortic and saphenous vein production of PGI2 were inhibited by 50% compared with PGI, produced by vascular tissues of control subjects who received no aspirin preoperatively (51 ± 10 pg 6-keto-PGF1J/mg aortic wet weight [mean + SEM] in aspirin-treated subjects vs 130 ± 16 pg/mg in control subjects, and 71 + 8 pg/mg saphenous vein wet weight vs 131 + 17 pg/mg). Blood loss at surgery was not significantly increased by preoperative low-dose aspirin as measured by chest tube drainage (754 ± 229 ml in aspirin-treated subjects vs 645 + 271 ml in control subjects), hematocrit nadir (31.

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“…HDL and LDL are also present in interstitial fluid and in lymph (Roheim et al, 1976 (Eldor et al, 1981). However, medial smooth muscle cells migrate through the internal elastic membrane and proliferate to form a neointima; these cells are capable of synthesizing PGI 2 and are in direct contact with plasma HDL and LDL (Eldor et al, 1981).…”

mentioning

confidence: 99%

“…Both HDL and LDL are normally transported through the intact endothelium of blood vessels by the process of diacytosis and come into contact with vascular smooth muscle cells present in the media Leake andaggregation can initiate the formation of experimental atherosclerotic lesions, prostaglandin formation is initially reduced (Eldor et al, 1981). However, medial smooth muscle cells migrate through the internal elastic membrane and proliferate to form a neointima; these cells are capable of synthesizing PGI 2 and are in direct contact with plasma HDL and LDL (Eldor et al, 1981).…”

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confidence: 99%

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Stimulation of vascular smooth muscle cell prostacyclin and prostaglandin E2 synthesis by plasma high and low density lipoproteins.

Pomerantz¹,

Tall²,

Feinmark³

et al. 1984

Circulation Research

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SUMMARY. We studied the effects of plasma high density and low density lipoproteins upon the synthesis of prostacyclin and prostaglandin E 2 by vascular smooth muscle cells. Prostaglandin synthesis was measured in 24-hour cultures by radioimmunoassay of the stable metabolites of prostacyclin, 6-keto-prostaglandin F,, t and of prostaglandin E 2 . High density lipoproteins induced dose-dependent increases in the release of 6-keto-prostaglandin F,,, and of prostaglandin E 2 from smooth muscle cells to values 14-and 50-fold above control. Incubations with low density lipoproteins at comparable cholesterol concentrations also induced dose-dependent release of 6-keto-prostaglandin Fi,, and prostaglandin E^ but to a lesser extent. Rat high density lipoprotein, which contained 2.5 times more cholesteryl arachidonate than human high density lipoproteins, stimulated 6-keto-prostaglandin Fi,, and prostaglandin E 2 release 2-to 3-fold more than human high density lipoproteins, whereas the delipidated apoproteins of high density lipoproteins had no significant effect on prostaglandin synthesis. II) with high density lipoprotein in stimulation of prostaglandin synthesis. The data indicate that both high and low density lipoproteins stimulate the synthesis of prostacyclin and prostaglandin E 2 by vascular smooth muscle cells. The results suggest that the lipoproteins provide arachidonate to a phospholipase-sensibve pool accessible to cyclooxygenase. (Circ Res 54: 554-565, 1984) PROSTACYCLIN (PGI 2 ) and prostaglandin E 2 (PGE 2 ) are vasodilator prostaglandins that are synthesized by blood vessels and vascular endothelial and smooth muscle cells grown in tissue culture (Moncada et al., 1977(Moncada et al., , 1979Weksler et al., 1977;Baenziger et al., 1979). Studies in perfused organs and in intact animals have indicated that the synthesis of PGI 2 and PGE 2 in vessels of organs such as the heart and kidneys, modulates the effects of vasoconstrictor stimuli, thus contributing to the maintenance of tissue perfusion (McGiff et al., 1970; Needleman et al., 1978;Oliver et al., 1980;Gunther and Cannon, 1980). Furthermore, Moncada and Vane have postulated that the balance between the production of thromboxane A 2 by platelets and the synthesis of PGI 2 by endothelial cells is important in the maintenance of vascular integrity (Moncada and Vane, 1979).The principal substrate for prostaglandin synthesis is arachidonate present in the phospholipids of cellular membranes; various mechanical and hormonal stimuli activate cell membrane phospholipases which liberate arachidonate, making it available to cyclooxygenase and other enzymes of the prostaglandin cascade (Ramwell et al., 1977;Whorton et al., 1982;and Hong and Deykin, 1982). However, arachidonate might also be derived from exogenous sources, and, in plasma, large amounts of arachidonic acid are present in esterified form in the phospholipids and cholesteryl esters of the plasma lipoproteins. In a previous study, we demonstrated that high density lipoproteins (HDL) markedly stim...

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Recovery of prostacyclin production by de-endothelialized rabbit aorta. Critical role of neointimal smooth muscle cells.

Cited by 166 publications

References 30 publications

Regional variability of prostacyclin biosynthesis.

Regional variability of prostacyclin biosynthesis.

Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

Stimulation of vascular smooth muscle cell prostacyclin and prostaglandin E2 synthesis by plasma high and low density lipoproteins.

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