Effects of Shear Stress on Eicosanoid Gene Expression and Metabolite Production in Vascular Endothelium as Studied in a Novel Biomechanical Perfusion Model

Doroudi, Roya; Gan, Li‐Ming; Sjögren, Lena Selin; Jern, Sverker

doi:10.1006/bbrc.2000.2279

Cited by 58 publications

(44 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although it has been proposed that PGIS preferentially couples with COX-2 for the production of PGI2 (Ueno et al 2001) in cultured cells, our data have indicated that PGIS would be up-regulated mainly with COX-1 in HUVECs exposed to E 2 in accordance with a published outcome for sheep (Rupnow et al 2002). TXAS, in turn, can be up-regulated along with COX-2 (Doroudi et al 2000), and COX-2 can be up-regulated by TXA2 (Caughey et al 2001), suggesting a closer relationship between COX-2 and TXAS. In our results, both COX-2 and TXAS remained unaltered after exposure to E 2 .…”

Section: Discussionsupporting

confidence: 82%

Estradiol selectively stimulates endothelial prostacyclin production through estrogen receptor-α

Sobrino¹,

Oviedo²,

Novella³

et al. 2010

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Estradiol (E 2 ) acts on the endothelium to promote vasodilatation through the release of several compounds, including prostanoids, which are products of arachidonic acid metabolism. Among these, prostacyclin (PGI2) and thromboxane A2 (TXA2) exert opposite effects on vascular tone. The role of different estrogen receptors (ERs) in the PGI2/TXA2 balance, however, has not been fully elucidated. Our study sought to uncover whether E 2 enhances basal production of PGI2 or TXA2 in cultured human umbilical vein endothelial cells (HUVECs), to analyze the enzymatic mechanisms involved, and to evaluate the different roles of both types of ERs (ERa and ERb). HUVECs were exposed to E 2 , selective ERa (1,3,5-tris(4-hydroxyphenyl)-4-propyl-1h-pyrazole, PPT) or ERb (diarylpropionitrile, DPN) agonists and antagonists (unspecific: ICI 182 780; specific for ERa: methyl-piperidino-pyrazole, MPP). PGI2 and TXA2 production was measured by ELISA. Expression of phospholipases, cyclooxygenases (COX-1 and COX-2), PGI2 synthase (PGIS), and thromboxane synthase (TXAS) was analyzed by western blot and quantitative RT-PCR. E 2 (1-100 nM) dose dependently increased PGI2 production (up to 50%), without affecting TXA2 production. COX-1 and PGIS protein and gene expressions were increased, whereas COX-2, phospholipases, and TXAS expression remained unaltered. All these effects were mediated through ERa, since they were produced not only in the presence of E 2 , but also in that of PPT, while they were abolished in the presence of MPP. In conclusion, E 2 , acting through ERa, up-regulates COX-1 and PGIS expression, thus directing prostanoid balance toward increased PGI2 production.

show abstract

Section: Discussionsupporting

confidence: 82%

Estradiol selectively stimulates endothelial prostacyclin production through estrogen receptor-α

Sobrino¹,

Oviedo²,

Novella³

et al. 2010

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…For example, shear stress induces PGHS-1 in human umbilical vein endothelial cells. 14 In addition, there are a number of putative promoter response elements for PGHS-1, including shear stress elements and transcription factor sites. 15 PGHS-2 is considered the inducible isoform (Ϸ72 kDa MW) whose expression is increased by a number of cardiovascular risk factors, such as cytokines, cholesterol, lipoproteins, and hypoxia.…”

Section: Regulation Of Pghs Expression In Vascular Cellsmentioning

confidence: 99%

Prostaglandin H Synthase and Vascular Function

Davidge

2001

Circulation Research

207

170

View full text Add to dashboard Cite

Abstract-Prostaglandin H synthase (PGHS) is a rate-limiting enzyme in the production of prostaglandins and thromboxane, which are important regulators of vascular function. Under normal physiological conditions, PGHSdependent vasodilators (such as prostacyclin) modulate vascular tone. However, PGHS-dependent vasoconstriction (mediated by thromboxane and/or its immediate precursor, PGH 2 ) predominates in some vascular pathologies (eg, systemic hypertension, diabetes, cerebral ischemia, and aging). This review will discuss the role of PGHS-dependent modulation of vascular function in a number of vascular beds (systemic, pulmonary, cerebral, and uterine) with an emphasis on vascular pathophysiology. Moreover, the specific contributions of the different isoforms (PGHS-1 and PGHS-2) are discussed. Understanding the role of PGHS in vascular function is of particular importance because they are the targets of the commonly used nonsteroidal antiinflammatory drugs (NSAIDs), which include aspirin and ibuprofen. Importantly, with the advent of specific PGHS-2 inhibitors for treatment of conditions such as chronic inflammatory disease, it is an opportune time to review the data regarding PGHS-dependent modulation of vascular function. (Circ Res. 2001;89:650-660.)

show abstract

“…Actually, both COX isoenzymes share characteristics of constitutive and inducible enzymes in endothelium. Shear stress induces COX-1 gene expression in human umbilical vein endothelial cells (HUVEC) (Doroudi et al, 2000), while clinical studies with a selective inhibitor of COX-2 (celecoxib) have shown that this enzyme exerts control of most systemic prostacyclin production in healthy humans (McAdam et al, 1999).…”

Section: Prostanoids In Endotheliummentioning

confidence: 99%