Prostacyclin-mediated effect of high density lipoproteins as cellular cholesterol acceptors on aortic smooth muscle cells

Shakhov, Y u; Larrue, J; Perova, N. V.; Dorian, B.; Daret, Danièle; Shcherbakova, Irina V.; Bricaud, H; Oganov, Raphael G.

doi:10.1016/0022-2828(89)90786-4

Cited by 9 publications

(2 citation statements)

References 29 publications

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“…HDL 3 has a higher cholesteryl arachidonate content than does HDL 2 and thus, the former may provide a larger supply of substrate for Cox enzymatic activity. 10,13 On the other hand, ASA pretreatment significantly reduced PGI 2 release induced by HDL. Thus, HDL may promote SMC PGI 2 synthesis acting as a substrate donor and as an inducer of Cox-2.…”

Section: Discussionmentioning

confidence: 99%

“…8 -12 In contrast, the effect of low density lipoprotein (LDL) on the biosynthesis of prostanoids is unclear: they can stimulate, inhibit, or have no effect on prostanoid synthesis. [11][12][13][14][15] This variable effect of LDL has been related to its degree of oxidation. 16,17 PGI 2 is a vasodilator prostaglandin that is synthesized by blood vessels and contributes to the maintenance of vascular tone.…”

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confidence: 99%

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Regulatory Effects of HDL on Smooth Muscle Cell Prostacyclin Release

Viñals¹,

Martı́nez-González²,

Badimon³

1999

ATVB

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Abstract-One mechanism by which high density lipoproteins (HDLs) exert their protective effect against coronary artery disease could be related to the induction of prostacyclin (PGI 2 ) release in the vessel wall. We have recently shown that HDL increases PGI 2 production in rabbit smooth muscle cells (RSMCs) and that this increase is dependent on cyclooxygenase-2 (Cox-2). Here we analyze the mechanism by which rabbit HDL induces PGI 2 release in RSMCs. Our results show that although HDL 2 and HDL 3 share a similar capacity to induce Cox-2 protein levels, HDL 3 stimulates a higher PGI 2 release than does HDL 2 , probably because of their relative arachidonate contents. Acetylsalicylic acid pretreatment (300 mol/L, 30 minutes) significantly reduced the HDL-induced PGI 2 release, suggesting that both preexisting and induced Cox-2 activities were involved in the HDL effect. Ca 2ϩ -dependent cytosolic phospholipase A 2 (cPLA 2 ) and Cox-1 protein levels were not altered by HDL. Dexamethasone (2 mol/L), which also inhibited the HDL-induced PGI 2 release, reduced significantly both Cox-2 mRNA and protein levels without affecting cPLA 2 and Cox-1 protein levels. In addition, methylarachidonyl fluorophosphonate, a potent inhibitor of cPLA 2 , did not produce any effect on HDL-induced PGI 2 release. In the presence of cycloheximide, Cox-2 mRNA levels were induced by HDL and inhibited by dexamethasone, suggesting that HDL and dexamethasone work in the absence of de novo protein synthesis. These results indicate an early effect of HDL on PGI 2 biosynthesis, specifically increasing Cox-2. PD98059, an inhibitor of mitogen-activated protein kinase kinase, completely inhibited HDL-induced PGI 2 release, whereas GF109203X, a protein kinase C inhibitor, had no effect. Thus, HDL induces PGI 2 synthesis by a mechanism dependent on the mitogen-activated protein kinase pathway but independent of protein kinase C.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Regulatory Effects of HDL on Smooth Muscle Cell Prostacyclin Release

Viñals¹,

Martı́nez-González²,

Badimon³

1999

ATVB

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Cyclooxygenase and 5‐lipoxygenase pathways in the vessel wall: Role in atherosclerosis

Vilá

2004

Medicinal Research Reviews

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Prostaglandins (PGs), thromboxanes (Txs), and leukotrienes (LTs) play a relevant role in cardiovascular physiology and pathophysiology. Recent reports concerning cardiovascular risk associated with cyclooxygenase-2 selective inhibitors have prompted questions about the "protective" or "deleterious" role of each COX isoform in cardiovascular disease, and the cloning and expression of inducible PGE-synthase (PGES) open the possibility that PGES could be a new therapeutical target in this context. Predominance of constricting or relaxing prostanoids depends not only on COX activity but also to downstream enzymes such as PGI-synthase (PGIS) and PGES. In the vessel wall, PGIS and PGES seem to be major downstream enzymes in the endothelium and smooth muscle, respectively. Like COX, activity of these enzymes can also be regulated by several factors, which include nitrogen oxides, cytokines, and lipid peroxides. LTs are important inflammatory mediators also involved in the pathophysiology of cardiovascular disease, which are targets for pharmacological intervention. Unlike COX pathway, the biosynthesis of chemotactic and vaso-constrictor LTs in the vasculature strongly depends on leukocyte recruitment and activation, and on cell-cell interaction between leukocytes and vascular cells in the inflamed areas. The present review emphasizes the role of vascular-derived prostanoids and LTs on atherosclerosis.

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