© 1997 American Heart Association, Inc.
Articles |
Induction of Cyclooxygenase-2 in Human Saphenous Vein and Internal Mammary Artery
From the Department of Applied Pharmacology (D.B.-B., S.W.L.) and Department of Thoracic Medicine (E.-B.H., R.N.), National Heart and Lung Institute, Imperial College of Science, Technology and Medicine; and Department of Cardiothoracic Surgery (J.R.P.) and Department of Anaesthetics and Critical Care Medicine (J.A.M.), Royal Brompton National Heart and Lung Hospital, London, UK.
Correspondence to Dr Jane A. Mitchell, Department of Anaesthetics and Critical Care Medicine, Royal Brompton National Heart and Lung Hospital, Sydney Street, London SW3 6NP, UK.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Abstract Within vessels, cyclooxygenase (COX) is expressed constitutively (COX-1) in endothelial cells where its production of prostacyclin is thought to contribute to the maintenance of vascular integrity. Recently, a novel isoform of COX, COX-2, has been described that is induced in animal arterial vessels after physical damage or exposure to proinflammatory cytokines. However, induction of COX-2 in human vessels has not been characterized. Moreover, the relative ability of arteries and veins to express COX-2 has not been addressed. Thus, we have compared the ability of segments of human saphenous vein and internal mammary artery, obtained from the same patient, to express COX-2 activity and mRNA after organ culture in the presence and absence of interleukin-1ß. COX-2 metabolites, measured by radioimmunoassay, were released by both the internal mammary artery and saphenous vein in the following rank order: prostaglandin E2
prostacyclin thromboxane
A2. Inclusion of interleukin-1ß in the culture medium
increased the release of prostanoids by the saphenous vein but not by
the internal mammary artery. However, the selective COX-2
inhibitor NS-398 significantly attenuated prostacyclin
release from both tissues. Northern blot analysis showed no
detectable COX-2 mRNA in freshly prepared saphenous vein or internal
mammary artery. In contrast, after 48 hours in organ culture, low
levels of COX-2 mRNA were detected in both internal mammary artery and
saphenous vein, an effect that was greatly increased by
interleukin-1ß. These observations show that COX-2 is induced in
human saphenous vein and internal mammary artery and suggest that this
may occur in humans after coronary artery bypass graft surgery.
The induction of COX-2 and subsequent release of prostacyclin may
represent an endogenous defense mechanism against
endothelial damage incurred during surgical preparation
of these vessels for bypass.
Key Words: cyclooxygenase • saphenous vein • internal mammary artery • prostacyclin
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The SV and IMA are the most commonly used CABG conduits. SV grafts are used for multiple bypass operations but are considered inferior to the IMA because they have reduced short-term and long-term patency. The poorer results seen with the SV are often caused by accelerated atherosclerosis, a reocclusion associated with a greater occurrence of angina, fatal infarcts, and reduced patient survival.1 Consequently, when the SV is used, reoperation is usually required within 10 years.2 The initiation of atherosclerosis is thought to involve damage to the vessel and/or the loss of a functional endothelium,3 resulting in a reduced release of protective mediators and subsequent platelet activation. One such important protective, "antiatherogenic" mediator is PGI2.4 PGI2 is a vasodilator with potent inhibitory actions on platelet function4 5 6 and is considered to be an endogenous antilipidemic agent.7 Indeed, it has previously been suggested that elevating the release of PGI2 or using exogenous PGI2 mimetics may be a therapeutic approach against cardiovascular diseases such as atherosclerosis.7
In healthy vessels, PGI2 is formed predominantly in the endothelial layer by the actions of constitutive COX-1.8 However, animal studies have demonstrated that vessels damaged by angioplasty or pinch9 express a novel isoform of COX (COX-2),10 an event that may account for an increased release of protective PGI2.11 Furthermore, cytokines such as platelet- derived growth factor or IL-1ß, which stimulate prostanoid release12 13 or induce COX-29 14 in isolated vascular cells in culture, are expressed in human atherosclerotic lesions3 and can cause coronary artery intimal lesions in the pig.15 Thus, the possibility exists that CABG conduits such as the SV and IMA may express COX-2 as a consequence of trauma due to surgical preparation.
The induction of COX-216 17 18 in vivo is generally associated with deleterious responses such as plasma extravasation or hyperalgesia. However, under conditions in which endothelial damage or dysfunction occurs, the local induction of COX-2 and the subsequent release of PGI2 in the underlying smooth muscle and/or remaining endothelial cells may compensate for the reduced thrombo-resistance of that section of the vessel.
Our aim, therefore, was to determine whether human vessels have the capacity to express COX-2. To this end, we used an organ culture system to study freshly prepared segments of the SV and IMA from patients undergoing CABG surgery. In addition, we investigated the effect of IL-1ß, a putative proatherogenic cytokine, on further COX-2 induction in this system.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Materials
Human recombinant IL-1ß was obtained from Boehringer-Mannheim; Hybond-N filters and tritiated prostanoids were purchased from Amersham; NS-398 was purchased from Calbiochem; all cell culture media and supplements were supplied by GIBCO BRL; and all other reagents were from Sigma Chemical Co.
Patients
Segments of nondistended SV and IMA from patients undergoing
CABG surgery were obtained from the same patients (n=4; 3 men and 1
woman aged 59 to 68 years) for determination of prostanoid release and
from different patients (3 men aged 59 to 68 years for SV and 3 men
aged 56 to 71 years for IMA) for COX-2 mRNA measurements. Five
additional SV (3 men and 2 women aged 50 to 64 years) and IMA (4 men
and 1 woman aged 52 to 69 years) segments were obtained from different
patients. Data were compared either as data from SV and IMA from the
same patients (n=4) or as pooled data from the larger population (n=9).
Vessels were used regardless of the drug therapy that the patient was
receiving. Ethical permission was obtained from the Ethical Committee
of the Royal Brompton National Heart and Lung Hospital. All vessels
were used regardless of preoperative drug therapy or patient
history.
Organ Culture
Vessels were placed immediately into sterile pots containing
sterile PBS (pH 7.0 to 7.3) supplemented with penicillin (1000 IU/mL)
and streptomycin (0.1 mg/mL) (PBS Pen-Strep) and prepared
immediately. Vessel organ culture was based on a modification of
Soyombo et al.19 Briefly, under sterile tissue culture
conditions, vessels were dissected free from connective tissue and
washed in PBS Pen-Strep. Vessels were then cut into rings of 
2 to
3 mm width. Individual rings were then placed into sterile 48-well
plates containing 500 µL of DMEM containing 1 mmol/L
sodium pyruvate and phenol red, supplemented with Pen-Strep and 2
mmol/L glutamine. All tissue incubations were performed at
37°C in an atmosphere of 5% CO2, 95% O2
using a culture incubator. Vessels were then left to equilibrate for 1
hour before the medium was replaced with fresh medium containing drugs
or relevant vehicle.
Vessels were incubated with IL-1ß (10 ng/mL) and drug or vehicle for 2 days, with the medium and drugs replaced at 24 hours. At 24 and 48 hours, the medium was removed and samples were then frozen (-20°C) until prostanoid levels could be determined (less than 1 month). At the end of each experiment (48 hours), tissues were blotted dry and weighed, snap-frozen in liquid nitrogen, and stored at -80°C until Northern blot analysis could be performed (less than 1 week). NS-398 was dissolved in cell-culture grade dimethyl sulfoxide and diluted in DMEM; all other drugs were made up in sterile distilled water. These solutions were then filtered through a 0.2-µm filter, and all subsequent dilutions were made up in DMEM.
Prostanoid Determination
6-Keto PGF1
(the breakdown
product of PGI2), TXB2 (the breakdown
product of TXA2), and PGE2 were measured by
radioimmunoassay using commercial antibodies and tritiated prostanoids,
as previously described.8 20 None of the drugs used in the
present study interfered with the radioimmunoassays for any of the
prostanoids measured.
Northern Blot Analysis
Frozen tissue segments were crushed under liquid nitrogen, and
total RNA was isolated according to the method of Chomczynski and
Sacchi.21 Samples of total RNA were size fractionated on a
1% agarose/formaldehyde gel containing 20 mmol/L
morpholinosulfonic acid, 5 mmol/L sodium acetate, and
1 mmol/L EDTA, pH 7.0, and blotted onto Hybond-N filters
through capillary action with the use of a saline sodium citrate
(sodium chloride, 175.3 g/L; sodium citrate, 88.2
g/L).
The COX-2 probe used for Northern hybridizations was a 520-bp fragment
corresponding to bases 1297 to 1816, as described by Hla and
Neilson,14 cloned into pGEM5z (Promega). Sequence identity
was confirmed by double-stranded sequencing using Sequenase version 2.0
(Amersham). Prehybridizations and hybridizations were performed at
42°C with the probes labeled to 1.5 to 2x106 cpm/mL
in a buffer containing 50% formamide, 50 mmol/L Tris-HCl
(pH 7.5), 5x Denhardt's solution, 0.1% SDS, 5 mmol/L
EDTA, and 250 µg/mL denatured salmon sperm DNA. After
hybridization, the filters were washed to a stringency of 0.1x
SSC/0.1% SDS at 60°C for 30 minutes before exposure to Kodak
X-OMAT-S film. To control for differences in loading or transfer of the
RNA, the filters were hybridized with a 1272-bp fragment from rat GAPDH
cDNA.
Statistics
Unless otherwise stated, all comparisons were made by use of
Student's paired t test, and a value of P<.05
was taken as the level of significance.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Effect of IL-1ß on Prostanoid Release by Segments of SV
Isolated segments of SV from four patients who also provided IMA segments released detectable amounts of 6-keto PGF1
, PGE2, and TXB2
after 24 and 48 hours (Fig 1
) in organ
culture. IL-1ß (10 ng/mL) caused an increase in the release of
6-keto PGF1, PGE2, and
TXB2 that was significantly greater than control incubation
values at 48 hours (Fig 1B). 6-Keto PGF1 and
PGE2 were released in equal amounts over the first 24
hours, whereas PGE2 became the dominant prostanoid released
over the second 24-hour period. TXB2 was released in
10-fold lower amounts than 6-keto PGF1 at
both time points (Fig 1). In a larger group of nine patients, for whom
SV was provided alone or together with samples of IMA, IL-1ß
increased the release of 6-keto PGF1 in a
similar fashion to that seen in the four patients for whom both SV and
IMA segments were provided (control release at 48 hours, 2.6±0.5
ng · mL-1 ·
mg-1; release in the presence of IL-1ß at 48
hours, 10.5±1.6 ng · mL-1 ·
mg-1; P=.0003 by unpaired,
two-tailed t test; n=9).
|
Characterization of 6-Keto PGF1 Release
by Segments of SV
The release of 6-keto PGF1 by SV at 24
(data not shown) or 48 hours (Fig 2)
under control culture conditions was prevented by coincubation with
NS-398 (30 µmol/L). The release of 6-keto
PGF1 induced by IL-1ß was similarly
inhibited by NS-398 and greatly attenuated by coincubation with
dexamethasone (1 µmol/L) at 24 and 48 hours
(Fig 2).
|
Effect of IL-1ß on Prostanoid Release by Segments of
IMA
Isolated segments of IMA from the four patients who also provided
SV segments released detectable amounts of 6-keto
PGF1, PGE2, and TXB2
after 24 and 48 hours (Fig 3). When
IL-1ß (10 ng/mL) was included in incubations of IMA, no
significant increase in the release of 6-keto
PGF1, PGE2, or TXB2
was observed at 24 or 48 hours (Fig 3). 6-Keto
PGF1 and PGE2 were released in
equal amounts throughout the study period, whereas the release of
TXB2 was 10-fold lower. We observed a large variation in
the ability of the IMA to release prostanoids in response to IL-1ß.
This variation consisted of a large (25-fold) stimulated release in the
presence of IL-1ß by the IMA from one patient and modest increases
(1.2-, 1.5-, and 3-fold increases over basal) from the other three
patients (Fig 3). Similarly, we found a variation in the ability of
NS-398 to inhibit 6-keto PGF1 release by IMA
cultured in the presence and absence of IL-1ß. Under control culture
conditions in three of the four patients, NS-398 inhibited 6-keto
PGF1 release (by 25%, 70%, and 90%,
respectively); however, 6-keto PGF1 release
in the remaining patient was increased by 33% in the presence of
NS-398. In the presence of IL-1ß, the release of 6-keto
PGF1 by IMA was significantly
(P<.05; one-sample t test) inhibited in the
presence of NS-398 (by 56±14%; n=4).
|
In a larger group of nine patients, for whom IMA segments were provided
alone or together with samples of SV, IL-1ß tended to increase the
release of 6-keto PGF1 in a similar fashion
to that seen in the four patients for whom both SV and IMA samples were
provided (control release at 48 h, 1.1±0.3 ng ·
mL-1 · mg-1;
release in the presence of IL-1ß at 48 hours, 4.7±2.6 ng ·
mL-1 · mg-1;
P>.05 by unpaired, two-tailed t test).
Northern Blot Analysis of SV and IMA Segments After 48
Hours of Organ Culture
No message for COX-2 was detected in freshly isolated segments of
SV and IMA, which were prepared immediately (Fig 4). However, under control culture
conditions, COX-2 message was detected in both SV and IMA, levels of
which were elevated when IL-1ß was included (Fig 4).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
To investigate the changes in COX-2 activity and expression in bypass conduits after CABG surgery, we studied isolated segments of SV and IMA from the same patients using an organ culture system. After 2 consecutive days in culture, segments of SV and IMA released prostanoids in the order of PGE2
prostacyclinTXA2, and these segments
contained detectable COX-2 mRNA. These results are consistent
with the reported high expression of prostacyclin synthase and low
expression of TX synthase in vascular smooth muscle22 23
and the ability of PGE2 to be formed
nonenzymatically.24 Interestingly, we did not detect mRNA
for COX-2 in freshly removed SV or IMA, indicating that vessels from
patients, even those with underlying coronary artery disease,
do not have a basal expression of COX-2 at the time of surgery. In
animal models, mild physical trauma causes COX-2 induction in vivo in
rat carotid arteries.9 Thus, the induction of COX-2 we
observed in the SV and IMA after 48 hours in organ culture is probably
the result of physical trauma applied to the vessel during the
necessary surgical procedure.25 In addition to tissue damage, cytokines believed to be involved in vascular disease, such as IL-1ß,3 15 induce COX-2 activity in various human cell types, including umbilical vein endothelial cells14 and pulmonary epithelial cells.26 Similarly, other inflammatory stimuli such as bacterial lipopolysaccharides induce COX-2 activity in murine8 and human27 macrophages and in segments of rat, rabbit, and human vessels in organ culture.28 When IL-1ß was included in our culture medium, mRNA for COX-2 was greatly enhanced in both SV and IMA. Thus, it is likely that local inflammatory events after surgery, leading to the release of cytokines such as IL-1ß, amplify the induction of COX-2 in the vessel.
Interestingly, we found that although the elevated induction of COX-2 mRNA by IL-1ß was consistent in both SV and IMA, the release of prostanoids by the SV was significantly greater than by the IMA. Furthermore, the release of prostanoids by the SV in the presence or absence of IL-1ß and by IMA treated with IL-1ß but not under control culture conditions was consistently inhibited by the specific COX-2 inhibitor NS-398.29 The variable results for COX-2 activity in IMA segments from the same patients, reported in the present study, may represent a failing in the translation of message to active COX-2 protein. Alternatively, because the rate-limiting step in the formation of COX metabolites is usually the liberation of the substrate, arachidonic acid, by phospholipase A2 activity,10 these observations may be explained by a differential regulation of phospholipase A2 in SV and IMA.
The consequence of COX-2 induction in these vessels is not known. Endogenous PGI2 release is considered beneficial in the cardiovascular system, where it is a vasodilator4 and an inhibitor of smooth muscle proliferation,30 cholesterol accumulation,7 31 and platelet and inflammatory cell activation.7 Thus, an increased release of PGI2 as a result of COX-2 induction may compensate for a reduced capacity of the vessel to release prostanoids after endothelial damage. We should also consider the possibility that COX-2 induction will have different consequences in IMA than in SV. Indeed, the induction of COX-2 may have detrimental effects in the SV, in which endogenously released prostanoids cause vasoconstriction.32 In contrast, the endogenous prostanoids released by the IMA are vasodilators.32 This discrepancy is indicative of differing prostanoid receptor subtypes between SV and IMA.
One feature of the SV and IMA in organ culture,29 similar to animal models33 34 and cultured cells,35 is the elevated release of PGE2, often accompanied by a decrease in PGI2. This shift in prostanoid production may be the result of a saturation of prostacyclin synthase, a change in intracellular oxidant tone, or an inhibition of prostacyclin synthase by lipid hydroperoxides.35 IMA grafts are generally stable, whereas SV grafts often require reoperation as a consequence of accelerated atherosclerosis.1 The higher levels of prostanoid release and a predominance of PGE2 accompanied by reduced PGI2 in SV grafts may contribute to a buildup of cholesterol in the vessel.33 The change in ratio of these two prostanoids may therefore be an important contributory factor to the patency of the graft.
COX-2 is induced in bypass vessels in organ culture, and this induction can be enhanced by IL-1ß. If our observations are representative of the response of these vessels in patients after CABG surgery, COX-2 may be a novel therapeutic target to maintain bypass vessel patency. Thus, if COX-2 metabolites are protective, we would speculate that treating the SV with an agent such as IL-1ß before transplant might have therapeutic benefit. However, if COX-2 induction represents a contributory factor to the decreased patency of the grafts, the newly described COX-2 selective nonsteroidal anti-inflammatory drugs may be of potential use as a therapy after bypass surgery.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
This work was funded by the Wellcome Trust and the British Heart Foundation (PG/9131). D.B.-B. is the recipient of a British Heart Foundation studentship (FS/94078). E.-B.H. is funded by a postdoctoral fellowship from the European Union.
Received August 7, 1996; accepted November 29, 1996.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Angelini GD, Newby AC. The future of saphenous vein as a coronary artery bypass conduit. Eur Heart J. 1989;10:273-280.
2.
Izzat MB, West RR, Bryan AJ, Angelini GD.
Coronary artery bypass surgery: current practice in the United
Kingdom. Br Heart J. 1994;71:382-385.
3. Ross R. Atherosclerosis: a defense mechanism gone awry. Am J Pathol. 1993;143:987-1002.[Medline] [Order article via Infotrieve]
4. Moncada S, Gryglewski R, Bunting S, Vane JR. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature. 1976;263:663-665.[Medline] [Order article via Infotrieve]
5. Radomski MW, Palmer RMJ, Moncada S. The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol. 1976;92:181-187.[Medline] [Order article via Infotrieve]
6.
Sneddon JM, Vane JR.
Endothelial derived relaxing factor reduces
platelet adhesion to bovine endothelial
cells. Proc Natl Acad Sci U S A. 1988;85:2800-2804.
7. Willis AL, Smith DL, Vigo C. Suppression of principal atherosclerotic mechanisms by prostacyclins and other eicosanoids. Prog Lipid Res. 1986;25:645-666.[Medline] [Order article via Infotrieve]
8.
Mitchell JA, Akarasereenont P, Thiemermann C, Flower
RJ, Vane JR. Selectivity of nonsteroidal anti-inflammatory drugs
as inhibitors of constitutive and inducible
cyclooxygenase. Proc Natl Acad Sci
U S A. 1993;90:11693-11697.
9.
Rimarachin JA, Jacobson JA, Szabo P, Maclouf J,
Creminon C, Weksler BB. Regulation of
cyclooxygenase-2 expression in aortic smooth muscle
cells. Arterioscler Thromb. 1994;14:1021-1031.
10. Mitchell JA, Larkin SW, Williams TJ. Cyclo-oxygenase-2: regulation and relevance in inflammation. Biochem Pharmacol. 1995;50:1535-1542.[Medline] [Order article via Infotrieve]
11. Eldor A, Falcone DJ, Hajjar DP, Minick CR, Weksler BB. Recovery of prostacyclin production by deendothelialized rabbit aorta: critical role of the neointimal smooth muscle cells. J Clin Invest. 1981;67:735-741.
12. Albrightson CR, Baenziger NL, Needleman P. Exaggerated human vascular cell prostaglandin biosynthesis mediated by monocytes: role of monokines and interleukin-1. J Immunol. 1985;135:1872-1877.[Abstract]
13. Libby P, Warner SJC, Friedman GB. Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J Clin Invest. 1988;81:487-498.
14.
Hla T, Nielson K. Human
cyclo-oxygenase-2 cDNA. Proc Natl Acad Sci
U S A. 1992;89:7384-7388.
15. Shimokawa H, Ito A, Fukumoto Y, Kadokami T, Nakaike R, Sakata M, Takayanagi T, Egashira K, Takeshita A. Chronic treatment with interleukin-1ß induces coronary intimal lesions and vasospastic responses in pigs in vivo. J Clin Invest. 1996;97:769-776.[Medline] [Order article via Infotrieve]
16.
Vane JR, Mitchell JA, Appleton I, Tomlinson A,
Bishop-Bailey D, Croxtall J, Willoughby DA. Inducible isoforms
of cyclooxygenase and nitric oxide synthase in
inflammation. Proc Natl Acad Sci U S A. 1994;91:2046-2050.
17.
Masferrer JL, Zweifel BS, Manning PT, Hauser SD, Leahy
KM, Smith WG, Isakson PC, Seibert K. Selective inhibition of
inducible cyclo-oxygenase 2 in vivo is anti-inflammatory
and nonulcerogenic. Proc Natl Acad Sci U S A. 1994;91:3228-3232.
18. Tomlinson A, Appleton I, Moore AR, Gilroy DW, Willis D, Mitchell JA, Willoughby DA. Cyclo-oxygenase and nitric oxide synthase isoforms in rat carrageenan-induced pleurisy. Br J Pharmacol. 1994;113:693-698.[Medline] [Order article via Infotrieve]
19. Soyombo AA, Angelini GD, Bryan AJ, Jasani B, Newby AC. Intimal proliferation in an organ culture of human saphenous vein. Am J Pathol. 1990;137:1401-1410.[Abstract]
20. Akarasereenont P, Mitchell JA, Bakhle YS, Thiemermann C, Vane JR. Comparison of induction of cyclooxygenase and nitric oxide synthase by endotoxin in endothelial cells and macrophages. Eur J Pharmacol. 1995;273:121-128.[Medline] [Order article via Infotrieve]
21. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162:156-159.[Medline] [Order article via Infotrieve]
22. Kerstein MD, Saroyan M, McMullen-Laird M, Hyman AL, Kadowitz P, McNamara DB. Metabolism of prostaglandins in human saphenous vein. J Surg Res. 1983;35:91-100.[Medline] [Order article via Infotrieve]
23. DeWitt DL, Smith WL. Purification of PGI2 synthase by immunoaffinity chromatography: evidence that the enzyme is a hemoprotein. J Biol Chem. 1983;285:3285-3293.
24. Smith WL, Marnett LJ, DeWitt DL. Prostaglandin and thromboxane biosynthesis. Pharmacol Ther. 1991;49:153-179.[Medline] [Order article via Infotrieve]
25. Holt CM, Francis SE, Newby AC, Rogers S, Gadsdon PA, Taylor T, Angelini GD. Comparison of response to injury in organ culture of human saphenous vein and internal mammary artery. Ann Thorac Surg. 1993;55:1522-1528.[Abstract]
26. Mitchell JA, Belvisi M, Akarasereenont P, Robbins R, Kwon O-J, Croxtall J, Barnes PJ, Vane JR. Induction of cyclo-oxygenase-2 by cytokines in human pulmonary epithelial cells: regulation by dexamethasone. Br J Pharmacol. 1994;113:1008-1014.[Medline] [Order article via Infotrieve]
27.
Fu JY, Masferrer JL, Seibert K, Raz A, Needleman
P. The induction and suppression of prostaglandin
H2 synthase (cyclooxygenase) in
human monocytes. J Biol Chem. 1990;265:16737-16740.
28. Bishop-Bailey D, Larkin SW, Griffiths MJD, Swain J, Pepper JR, Williams TJ, Mitchell JA. Characterisation of prostacyclin (PGI2) and prostaglandin E2 (PGE2) release from human saphenous vein in response to bacterial LPS. Br J Pharmacol. 1995;115:P136. Abstract.
29. Futaki N, Takahashi S, Yokoyama M, Arai I, Higuchi S, Otomo S. NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin synthase/cyclooxygenase (COX-2) activity in vitro. Prostaglandins. 1994;47:55-59.[Medline] [Order article via Infotrieve]
30. Hara S, Morishita R, Tone Y, Yokoyama C, Inoue H, Kaneda Y, Ogihara T, Tanabe T. Overexpression of prostacyclin synthase inhibits growth of vascular smooth muscle cells. Biochem Biophys Res Commun. 1995;216:862-867.[Medline] [Order article via Infotrieve]
31. Hajjar DP, Pomerantz KB. Signal transduction in atherosclerosis: integration of cytokines and the eicosanoid network. FASEB J. 1992;6:2933-2941.[Abstract]
32.
Yang Z, von Segesser L, Bauer E, Stulz P, Turina M,
Luscher TF. Different activation of the
endothelial L-arginine and
cyclooxygenase pathway in the human internal
mammary artery and saphenous vein. Circ Res. 1991;68:52-60.
33. Subbiah MTR. Prostaglandin E2 biosynthesis and effect in pigeon aorta. Atherosclerosis. 1978;29:487-495.[Medline] [Order article via Infotrieve]
34. Berberian PA, Ziboh VA, Hsia SL. Inhibition of cholesterol esterification in rabbit aorta by prostaglandin E2. Atherosclerosis. 1977;27:213-220.[Medline] [Order article via Infotrieve]
35. Ager A, Gordon JL, Moncada S, Pearson JD, Salmon JA, Trevethick MA. Effects of isolation and culture on prostaglandin synthesis by porcine aortic endothelial and smooth muscle cells. J Cell Physiol. 1982;110:9-16.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  N. Foudi, L. Louedec, T. Cachina, C. Brink, and X. Norel Selective cyclooxygenase-2 inhibition directly increases human vascular reactivity to norepinephrine during acute inflammation Cardiovasc Res, February 1, 2009; 81(2): 269 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Harrington, R. Lucas, S. K. McMaster, L. Moreno, G. Scadding, T. D. Warner, and J. A. Mitchell COX-1, and not COX-2 activity, regulates airway function: relevance to aspirin-sensitive asthma FASEB J, November 1, 2008; 22(11): 4005 - 4010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-T. Hong, J. Huang, T. D. Barrett, and B. R. Lucchesi Effects of cyclooxygenase inhibition on canine coronary artery blood flow and thrombosis Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H145 - H155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bishop-Bailey, J. A. Mitchell, and T. D. Warner COX-2 in cardiovascular disease. Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 956 - 958. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Fosslien Cardiovascular Complications of Non-Steroidal Anti-Inflammatory Drugs Ann. Clin. Lab. Sci., October 1, 2005; 35(4): 347 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Takayama, G. Garcia-Cardena, G. K. Sukhova, J. Comander, M. A. Gimbrone Jr., and P. Libby Prostaglandin E2 Suppresses Chemokine Production in Human Macrophages through the EP4 Receptor J. Biol. Chem., November 8, 2002; 277(46): 44147 - 44154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bishop-Bailey, T. Hla, and T. D. Warner Intimal Smooth Muscle Cells as a Target for Peroxisome Proliferator-Activated Receptor-{gamma} Ligand Therapy Circ. Res., August 9, 2002; 91(3): 210 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. E. Caughey, L. G. Cleland, P. S. Penglis, J. R. Gamble, and M. J. James Roles of Cyclooxygenase (COX)-1 and COX-2 in Prostanoid Production by Human Endothelial Cells: Selective Up-Regulation of Prostacyclin Synthesis by COX-2 J. Immunol., September 1, 2001; 167(5): 2831 - 2838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Lazzeri, M. G. Belvisi, H. J. Patel, M. H. Yacoub, K. Fan Chung, and J. A. Mitchell Effects of Prostaglandin E2 and cAMP Elevating Drugs on GM-CSF Release by Cultured Human Airway Smooth Muscle Cells . Relevance to Asthma Therapy Am. J. Respir. Cell Mol. Biol., January 1, 2001; 24(1): 44 - 48. [Abstract] [Full Text]
|
|
|
|
|
|
S. J. Stanford, J. R. Pepper, and J. A. Mitchell Cyclooxygenase-2 Regulates Granulocyte-Macrophage Colony-Stimulating Factor, but Not Interleukin-8, Production by Human Vascular Cells : Role of cAMP Arterioscler. Thromb. Vasc. Biol., March 1, 2000; 20(3): 677 - 682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yamamoto, M. Aoyagi, N. Fukai, Y. Matsushima, and K. Yamamoto Increase in Prostaglandin E2 Production by Interleukin-1{beta} in Arterial Smooth Muscle Cells Derived From Patients With Moyamoya Disease Circ. Res., November 12, 1999; 85(10): 912 - 918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Schonbeck, G. K. Sukhova, P. Graber, S. Coulter, and P. Libby Augmented Expression of Cyclooxygenase-2 in Human Atherosclerotic Lesions Am. J. Pathol., October 1, 1999; 155(4): 1281 - 1291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Woods, J. A. Mitchell, E. G. Wood, S. Barker, N. R. Walcot, G. M. Rees, and T. D. Warner Endothelin-1 Is Induced by Cytokines in Human Vascular Smooth Muscle Cells: Evidence for Intracellular Endothelin-Converting Enzyme Mol. Pharmacol., May 1, 1999; 55(5): 902 - 909. [Abstract] [Full Text]
|
|
|
|
|
|
T. G. Brock, R. W. McNish, and M. Peters-Golden Arachidonic Acid Is Preferentially Metabolized by Cyclooxygenase-2 to Prostacyclin and Prostaglandin E2 J. Biol. Chem., April 23, 1999; 274(17): 11660 - 11666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Beasley COX-2 and cytosolic PLA2 mediate IL-1beta -induced cAMP production in human vascular smooth muscle cells Am J Physiol Heart Circ Physiol, April 1, 1999; 276(4): H1369 - H1378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Bishop-Bailey, J. R. Pepper, S. W. Larkin, and J. A. Mitchell Differential Induction of Cyclooxygenase-2 in Human Arterial and Venous Smooth Muscle : Role of Endogenous Prostanoids Arterioscler. Thromb. Vasc. Biol., October 1, 1998; 18(10): 1655 - 1661. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||