Cytokine-Induced Expression of Parathyroid Hormone-Related Peptide in Cultured Human Vascular Endothelial Cells

Abstract Rat pituitary malignant tumor cells; mGH3, show hypervascularization in in vivo xenografts and overexpress parathyroid hormone-related peptide (PTHrP) compared to original GH3 cells. To elucidate whether PTHrP is involved in tumor-derived angiogenesis, we examined the effect of PTHrP on vascular endothelial cells both in vitro and in vivo. Results of in vivodiffusion chamber assay showed a clear hypervascularization on the outer surface of diffusion chambers containing mGH3 tumor cell implants but not in those containing GH3 cells. Co-incubation with antisense PTHrP oligonucleotide (10 μM), but not sense or mismatched PTHrP oligonucleotide, suppressed hypervascularization in diffusion chambers. To further examine the role of PTHrP on endothelial cell function, PTHrP(1–34) was added at various concentrations to cultured bovine endothelial cells (BAECs) harvested from the aorta. PTHrP(1–34) did not alter the proliferation or migration of endothelial cells, but rather dose-dependently increased capillary formation by endothelial cells on the collagen gel matrix. Furthermore, 0.1 mM of 8-bromo-cAMP caused a similar increase in tube formation, which was dose-dependently inhibited by H89, a protein kinase A inhibitor. Our results indicate for the first time that PTHrP is a potential paracrine factor acting via the PKA pathway to enhance angiogenesis through capillary tube formation by endothelial cells in malignant pituitary tumors.

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INTERLEUKIN-10 INHIBITS IL-1β BUT NOT TNF-α INDUCED EXPRESSION OF ADHESION MOLECULES ON HUMAN VASCULAR ENDOTHELIAL CELLS

Shock ◽

10.1097/00024382-199703001-00196 ◽

1997 ◽

Vol 7 (Supplement) ◽

pp. 49

Author(s):

A Nooteboom ◽

Th Hendriks ◽

IHJTh de Hingh ◽

CJ van der Linden

Keyword(s):

Endothelial Cells ◽

Adhesion Molecules ◽

Vascular Endothelial Cells ◽

Interleukin 10 ◽

Vascular Endothelial ◽

Induced Expression ◽

Tnf Α

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Involvement of NADPH oxidase in oxidized LDL-induced upregulation of heat shock factor-1 and plasminogen activator inhibitor-1 in vascular endothelial cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.91023.2008 ◽

2009 ◽

Vol 297 (1) ◽

pp. E104-E111 ◽

Cited By ~ 26

Author(s):

Ruozhi Zhao ◽

Xiuli Ma ◽

Xueping Xie ◽

Garry X. Shen

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Oxidized Ldl ◽

Plasminogen Activator Inhibitor ◽

Heat Shock Factor 1 ◽

Vascular Endothelial ◽

Plasminogen Activator Inhibitor 1 ◽

Induced Expression ◽

Activator Inhibitor ◽

Pai 1

Plasminogen activator inhibitor-1 (PAI-1) is implicated in thrombogenesis, inflammation, and extracellular matrix remodeling. Previous studies indicated that oxidized low-density lipoprotein (LDL) stimulated the generation of PAI-1 in vascular endothelial cells (EC). The present study demonstrated that LDL oxidized by copper, iron, or 3-morpholinosydnonimine increased the expression of NADPH oxidase (NOX) 2, PAI-1, and heat shock factor-1 (HSF1) in human umbilical vein EC or coronary artery EC compared with LDL or vehicle. Diphenyleneiodonium, a NOX inhibitor, prevented the increases of the expression of HSF1 and PAI-1 in EC induced by oxidized LDLs. Small-interference RNA (siRNA) for p22phox, an essential subunit of NOX, prevented oxidized LDL-induced expression of NOX2, HSF1, and PAI-1 in EC. HSF1 siRNA inhibited oxidized LDL-induced expression of PAI-1 and HSF1, but not NOX2, in EC. The binding of HSF1 to PAI-1 promoter and the activity of PAI-1 promoter in EC were enhanced by oxidized LDL. Butylated hydroxytulene, a potent antioxidant, inhibited oxidized LDL-induced release of hydrogen peroxide (H2O2) and the expression of NOX2, HSF1, and PAI-1 in EC. Treatment with H2O2 increased the abundance of NOX2, HSF1, and PAI-1 in EC. The results of the present study indicate that oxidized LDL-induced expression of NOX may lead to the elevated release of reactive oxygen species, the activation of HSF1, and the enhancement of the transcription of PAI-1 gene in cultured vascular EC.

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