Vascular endothelial growth factor mRNA in pericytes is upregulated by phorbol myristate acetate.
- 1 January 1998
- journal article
- other
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 31 (1), 511-515
- https://doi.org/10.1161/01.hyp.31.1.511
Abstract
Increased microvascular permeability, which occurs in conditions such as the adult respiratory distress syndrome and diabetes mellitus, is related to physicochemical alterations in the microvascular barrier. We postulate that, in part, capillary pericytes affect microvascular permeability via production of a vasoactive cytokine, viz, vascular endothelial growth factor (VEGF), also known as vascular permeability factor. The goal of the present study was to evaluate the effects of phorbol myristate acetate (PMA), a substance known to produce nonhydrostatic pulmonary edema in intact animals, on VEGF gene expression in pericyte cultures. Microvascular pericytes were isolated from bovine retinas using magnetic microspheres coated with 3G5 monoclonal antibody. Pericyte identity was confirmed both morphologically and by immunostaining for α-smooth muscle actin and 3G5 ganglioside. The cultured pericytes were stimulated with N ω -nitro- l -arginine methyl ester (L-NAME, 1×10 −4 mmol/L), angiotensin II (1×10 −6 mmol/L), and PMA (5×10 −8 mmol/L), selected because of their ability to upregulate VEGF mRNA expressions in other cell types. Northern blot analysis was performed using [ 32 P]dCTP labeled human VEGF cDNA (Genentech). Lane-loading differences were normalized using mouse GAPDH control cDNA probe. VEGF mRNA expression was upregulated by PMA (10 −9 to 10 −6 mol/L) in a dose-dependent manner, whereas neither L-NAME nor angiotensin II affected VEGF mRNA expression in pericytes. These results support the hypothesis that pericytes increase permeability of the endothelial barrier through increased VEGF production.Keywords
This publication has 28 references indexed in Scilit:
- Glaucoma, Capillaries and PericytesOphthalmologica, 1996
- Human mesangial cells and peripheral blood mononuclear cells produce vascular permeability factorKidney International, 1993
- Update on the cellular and molecular basis of capillary permeabilityTrends in Cardiovascular Medicine, 1993
- Capillary pericytes: Perspectives and future trendsJournal of Electron Microscopy Technique, 1991
- Angiotensin II receptor-mediated proliferation of cultured human fetal mesangial cellsKidney International, 1991
- Vasoactive hormones and cAMP affect pericyte contraction and stress fibresin vitroJournal of Muscle Research and Cell Motility, 1988
- A monoclonal antibody (3G5)-defined ganglioside antigen is expressed on the cell surface of microvascular pericytes.The Journal of Experimental Medicine, 1988
- Phorbol myristate acetate stimulates formation of phosphatidyl inositol 4-phosphate and phosphatidyl inositol 4,5-bisphosphate in human plateletsBiochemical and Biophysical Research Communications, 1984
- Culture of retinal capillary cells using selective growth mediaMicrovascular Research, 1983
- Analysis of relationships between pericytes and gas exchange capillaries in neonatal and mature bovine lungsMicrovascular Research, 1983