Eicosanoids in regulation of arterial smooth muscle cell phenotype, proliferative capacity, and cholesterol metabolism.

Pomerantz, Kenneth B.; Hajjar, David P.

doi:10.1161/01.atv.9.4.413

Cited by 103 publications

(22 citation statements)

References 220 publications

(35 reference statements)

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“…As prostacycin, the major endothelium-derived prostanoid, is a vasoprotective, antithrombotic, antiplatelet, growth-suppressant molecule (14), the induction of COX-2 may be considered as another example of induction by lysoPC of a vasoprotective and potentially antiatherogenic endothelial gene. However, several reservations have to be made at this point because the role of cyclooxygenases and prostanoids in the pathogenesis of atherogenesis are currently poorly understood (30). Our results are consistent with observations demonstrating that oxidized LDL enhance the endothelial synthesis of prostacyclin (31,32) as well as COX-2 mRNA levels (33).…”

Section: Discussionsupporting

confidence: 90%

Induction of cyclooxygenase-2 in human umbilical vein endothelial cells by lysophosphatidylcholine.

Zembowicz

Jones²,

1995

J. Clin. Invest.

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Lysophosphatidyicholine (lysoPC), a component of atherogenic lipoproteins and atherosclerotic lesions, has been recently suggested to play a role in atherogenesis. LysoPC is known to induce several endothelial genes involved in leukocyte recruitment, mitogenesis, and inflammation. Cyclooxygenases (prostaglandin H2 synthases) are rate-limiting enzymes involved in the endothelial synthesis of prostacyclin, an antiplatelet, vasorelaxant, and vasoprotective molecule. We investigated the effect of lysoPC on the endothelial expression of cyclooxygenases. Our results demonstrate that, in cultured human umbilical vein endothelial cells, lysoPC induces cyclooxygenase-2 mRNA and protein levels. Increased expression of cyclooxygenase-2 is accompanied by the enhancement of both basal-and calcium ionophore A23187-induced synthesis of prostacyclin. Nuclear runoff experiments demonstrated an increased rate of transcription of the cyclooxygenase-2 gene by lysoPC. In contrast, lysoPC did not affect the expression of constitutive cyclooxygenase-1. Our results suggest that the induction of endothelial cyclooxygenase-2 by lysoPC may be an important vasoprotective mechanism that limits progression of atherosclerotic lesions and promotes their regression. (J.

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Section: Discussionsupporting

confidence: 90%

Induction of cyclooxygenase-2 in human umbilical vein endothelial cells by lysophosphatidylcholine.

Zembowicz

Jones²,

1995

J. Clin. Invest.

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“…Furthermore, the dramatic potentiation of the effects of IL-l, TNF and LPS by CAMP-elevating agents raises the possibility that some extracellular mediators which elevate the intracellular CAMP level have a role in the progress of the above diseases by the combination with IL-l, TNF and LPS. In vascular systems, endothelial cells, SMCs and macrophages produce prostaglandins Ez and 12, which elevate the CAMP level in SMCs [31]. Such prostanoids may also have some roles in the progress of inflammation in addition to the regulation of contraction of vascular smooth muscle.…”

Section: Resultsmentioning

confidence: 99%

Group II phospholipase A₂ mRNA synthesis is stimulated by two distinct mechanisms in rat vascular smooth muscle cells

et al. 1990

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Two potent inflammatory mediators, interleukin 1 (IL-l) and tumor necrosis factor (TNF) as well as lipopolysa~ha~de (LPS) increased group II phospholipase 4 (PL4) mRNA levels, which resulted in enhanced secretion of the PL4 enzyme from rat smooth muscle cells. CAMP-elevating agents also stimulated the release of PL4 and increased the mRNA, but IL-I, TNF and LPS did not affect CAMP levels. Furthermore, the effects of TNF and CAMP-elevating agents were not additive but synergistic. Therefore, we concluded that the level of rat group II PL4 mRNA is controlled at least by two distinct mechanisms, one involves CAMP and the other is mediated by TNF, IL-l and LPS. This study also suggests important roles of group II PLA, in pathogenesis of vascular inflammation.

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“…The detailed mechanism by which COX-2 inhibitors suppressed the Ang II-stimulated DNA and protein synthesis in rat VSMCs is uncertain, but increased production of PGs have been implicated to take part in modulation of cell proliferation in VSMCs. 31 Furthermore, COX-2 expression was shown to increase in rat VSMCs after balloon injury in vivo 32 and in response to serum or growth factors. 32,33 The overexpression of COX-2 in epithelial cells inhibits apoptosis.…”

Section: Discussionmentioning

confidence: 97%

Induction of Cyclooxygenase-2 by Angiotensin II in Cultured Rat Vascular Smooth Muscle Cells

et al. 2000

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Abstract-Angiotensin II (Ang II) stimulates the release of prostaglandins (PGs) in various cells and tissues. Recently, cyclooxygenase-2 (COX-2) emerged as a new key regulator for PG synthesis. In the present study, we investigated whether Ang II regulates COX-2 expression in cultured rat vascular smooth muscle cells (VSMCs). Ang II markedly increased the expression of COX-2 mRNA in a time-and dose-dependent manner. This effect was completely blocked by the Ang II type 1 receptor antagonist losartan but not by the Ang II type 2 receptor antagonist PD123319. The p42/44 mitogen-activated protein kinase (MAPK) kinase-1 inhibitor PD98059 and the p38 MAPK inhibitor SB203580 significantly suppressed Ang II-induced COX-2 mRNA and protein expression. Ang II did not increase transcription of the COX-2 gene, as examined with a COX-2 promoter/luciferase chimeric plasmid construct. Instead, it suppressed the degradation of COX-2 mRNA. PD98059 and SB203580 markedly enhanced the decay of COX-2 mRNA induced by Ang II, implying that p42/44 and p38 MAPK activated by Ang II play a role in the regulation of COX-2 through stabilization of its mRNA. The COX-2-specific inhibitor NS-398 attenuated Ang II-stimulated DNA and protein synthesis, as well as PGE 2 production by VSMCs. These results suggest that Ang II regulates COX-2 expression and PG production and modulates cell proliferation through MAPK-mediated signaling pathways in rat VSMCs.

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Eicosanoids in regulation of arterial smooth muscle cell phenotype, proliferative capacity, and cholesterol metabolism.

Cited by 103 publications

References 220 publications

Induction of cyclooxygenase-2 in human umbilical vein endothelial cells by lysophosphatidylcholine.

Induction of cyclooxygenase-2 in human umbilical vein endothelial cells by lysophosphatidylcholine.

Group II phospholipase A₂ mRNA synthesis is stimulated by two distinct mechanisms in rat vascular smooth muscle cells

Induction of Cyclooxygenase-2 by Angiotensin II in Cultured Rat Vascular Smooth Muscle Cells

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Eicosanoids in regulation of arterial smooth muscle cell phenotype, proliferative capacity, and cholesterol metabolism.

Cited by 103 publications

References 220 publications

Induction of cyclooxygenase-2 in human umbilical vein endothelial cells by lysophosphatidylcholine.

Induction of cyclooxygenase-2 in human umbilical vein endothelial cells by lysophosphatidylcholine.

Group II phospholipase A2 mRNA synthesis is stimulated by two distinct mechanisms in rat vascular smooth muscle cells

Induction of Cyclooxygenase-2 by Angiotensin II in Cultured Rat Vascular Smooth Muscle Cells

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Group II phospholipase A₂ mRNA synthesis is stimulated by two distinct mechanisms in rat vascular smooth muscle cells