Antimitotic actions of vasodilatory prostaglandins — clinical aspects

Sinzinger, H.; Fitscha, P; Kritz, H

doi:10.1007/978-3-0348-7352-9_5

Cited by 7 publications

(10 citation statements)

References 22 publications

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“…19,20 For instance, in advanced atherosclerosis, PGI 2 synthesis associated with activation of the COX-2 gene was significantly elevated in VSMCs of the plaque, in both the intima and the media. 21 Moreover, in enterocytes, the COX-2-selective antagonist SC58125 was shown to inhibit basal and lipopolysaccharide-stimulated 6-keto-PGF 1␣ levels but not PGE 2 , suggesting that PGI 2 production occurred mainly by a COX-2-dependent mechanism, whereas PGE 2 formation occurred via a COX-1-mediated mechanism. 22 PGI 2 has several vasoprotective effects, including vasodilation, anti-platelet aggregation, and inhibition of smooth muscle cell proliferation.…”

Section: Discussionmentioning

confidence: 94%

“…24 The latter data are consistent with studies showing that although PGI 2 is antimitogenic for VSMCs, tolerance can develop toward PGI 2 receptors in a number of experimental settings. 21,24 Possible desensitization at the receptor level also has been observed when iloprost therapy was administered to humans for 1 to 4 weeks. 21 In the present study, endogenous formation of COX-2-derived PGI 2 occurred after exposure of the cells to either Ang II or TNF-␣, a sequence that may have limited the antiproliferative effects of this prostanoid.…”

Section: Discussionmentioning

confidence: 96%

“…21,24 Possible desensitization at the receptor level also has been observed when iloprost therapy was administered to humans for 1 to 4 weeks. 21 In the present study, endogenous formation of COX-2-derived PGI 2 occurred after exposure of the cells to either Ang II or TNF-␣, a sequence that may have limited the antiproliferative effects of this prostanoid. However, the increase in COX-2-derived PGI 2 synthesis in VSMCs may be important in conditions such as Ang II-dependent hypertension, or other conditions associated with the infiltration of mononuclear cells, given that damage of endothelial cells may preclude the production of PGI 2 at the site of injury.…”

Section: Discussionmentioning

confidence: 96%

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Cyclooxygenase-2 Is Required for Tumor Necrosis Factor-α– and Angiotensin II–Mediated Proliferation of Vascular Smooth Muscle Cells

Young

Mahboubi

Haider

et al. 2000

Circulation Research

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Abstract-Tumor necrosis factor-␣ (TNF-␣) and angiotensin II (Ang II) induced a transient increase in vascular smooth muscle cell (VSMC) cyclooxygenase-2 (COX-2) mRNA accumulation, without affecting COX-1 mRNA levels. The kinetics of COX-2 mRNA accumulation were similar in VSMCs challenged with either TNF-␣ or Ang II; mRNA accumulation peaked at 2 hours and decreased to control levels by Ϸ6 hours. Accumulation of COX-2 mRNA was associated with a time-dependent increase of COX-2 protein expression that displayed similar kinetics in response to either TNF-␣ or Ang II. Both the increase in COX-2 mRNA accumulation and protein expression in response to either TNF-␣ or Ang II were inhibited by the mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor PD098059. In addition, the AT 1 -selective receptor antagonist losartan attenuated the Ang II-mediated increase in COX-2 mRNA accumulation; the AT 2 -selective antagonist PD123319 had no effect. Prostacyclin I 2 synthesis was tightly coupled to expression of COX-2, whereas prostaglandin E 2 and thromboxane A 2 (TXA 2 ) synthesis may be associated with differential usage of COX-1 and COX-2. The COX-2-selective inhibitors NS-398 and nimesulide and the TXA 2 receptor antagonist BMS 180,291 inhibited TNF-␣-and Ang II-mediated increases in DNA content and cell number by Ϸ95%. These findings suggest that a prostanoid derived from COX-2, possibly TXA 2 , may contribute to VSMC hyperplasia in vessel injury or pathophysiological conditions associated with elevated levels of either TNF-␣ or Ang II. (Circ Res. 2000;86:906-914.)

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Cyclooxygenase-2 Is Required for Tumor Necrosis Factor-α– and Angiotensin II–Mediated Proliferation of Vascular Smooth Muscle Cells

Young

Mahboubi

Haider

et al. 2000

Circulation Research

View full text Add to dashboard Cite

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“…[32][33][34] Infusions of PGI 2 or PGI 2 mimetics are used therapeutically in the management of primary pulmonary hypertension and peripheral vascular disease and as an alternative to heparin infusion in hemofiltration. It has also been reported that PGI 2 has antilipidemic properties 35 and antimitotic actions on vascular smooth muscle cells 36 and, thus, may be useful in the prevention/treatment of atherosclerosis. HDLs, the low plasma levels of which are indicative of atherogenesis, have been shown to increase COX-2 expression, inducing PGI 2 , in cytokine-stimulated endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2 Regulates Granulocyte-Macrophage Colony–Stimulating Factor, but Not Interleukin-8, Production by Human Vascular Cells

Stanford

Pepper

Mitchell

2000

ATVB

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Abstract-Vascular smooth muscle is now recognized as an important site of mediator generation under inflammatory conditions. Indeed, the release of leukocyte activators, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-8, by human arterial smooth muscle cells has recently been demonstrated. However, the potential for venous cells to release GM-CSF has not been addressed. We have shown that human vascular smooth muscle cells express the "inflammatory" form of cyclooxygenase (COX), cyclooxygenase-2 (COX-2), when stimulated with cytokines. In some nonvascular cell types, the COX activity has been shown to regulate the release of GM-CSF and IL-8, although the nature of the isoform responsible was not addressed. We show that human venous smooth muscle cells, like their arterial counterparts, release GM-CSF after stimulation with IL-1␤. Similarly, both cell types released IL-8. Under the same conditions, we found that COX-2 activity suppressed GM-CSF, but not IL-8, release by both types of human vascular cells. Moreover, the prostacyclin mimetic, cicaprost, and the cAMP analogue, dibutyryl cAMP, inhibited GM-CSF release from these cells. These observations suggest that COX-2 activity suppresses GM-CSF release via a cAMP-dependent pathway in human vascular cells and illustrates a novel mechanism by which this enzyme can modulate immune and inflammatory events.

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“…Thromboxane (TX)A 2 increases proliferation, and DNA and RNA synthesis in several cell types, including fibroblasts and smooth muscle like glomerular mesangial cells [13-16]. Conversely, prostacyclin (PGI 2 ) decreases smooth muscle cell proliferation and collagen synthesis [17,18]. …”

Section: Introductionmentioning

confidence: 99%

Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis

et al. 2002

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Background: Prostanoids are known to participate in the process of fibrogenesis. Because lung fibroblasts produce prostanoids and are believed to play a central role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), we hypothesized that fibroblasts (HF) cultured from the lungs of patients with IPF (HF-IPF) have an altered balance between profibrotic (thromboxane [TX]A 2 ) and antifibrotic (prostacyclin [PGI 2 ]) prostaglandins (PGs) when compared with normal human lung fibroblasts (HF-NL). Methods: We measured inducible cyclooxygenase (COX)-2 gene and protein expression, and a profile of prostanoids at baseline and after IL-1β stimulation. Results: In both HF-IPF and HF-NL COX-2 expression was undetectable at baseline, but was significantly upregulated by IL-1β. PGE 2 was the predominant COX product in IL-1β-stimulated cells with no significant difference between HF-IPF and HF- ] ng/10 6 cells/30 min, respectively; P = 0.25). TXB 2 (the stable metabolite of TXA 2 ) production was significantly higher in IL-1β-stimulated HF-IPF compared to HF-NL (1.92 [1.27-2.57] vs. 0.61 [0.21-1.64] ng/10 6 cells/30 min, respectively; P = 0.007) and the ratio of PGI 2 (as measured by its stable metabolite 6-keto-PGF 1α ) to TXB 2 was significantly lower at baseline in

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Antimitotic actions of vasodilatory prostaglandins — clinical aspects

Cited by 7 publications

References 22 publications

Cyclooxygenase-2 Is Required for Tumor Necrosis Factor-α– and Angiotensin II–Mediated Proliferation of Vascular Smooth Muscle Cells

Cyclooxygenase-2 Is Required for Tumor Necrosis Factor-α– and Angiotensin II–Mediated Proliferation of Vascular Smooth Muscle Cells

Cyclooxygenase-2 Regulates Granulocyte-Macrophage Colony–Stimulating Factor, but Not Interleukin-8, Production by Human Vascular Cells

Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis

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