Serum and Platelet-Derived Growth Factor-Induced Expression of Vascular Permeability Factor Mrna by Human Vascular Smooth Muscle Cells In Vitro

Abstract

1. Endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation are key events in the pathogenesis of atherosclerosis. Vascular permeability factor (VPF), an endothelial-cell-specific multifunctional cytokine, was recently described, and has the potential to contribute to the development of endothelial dysfunction. The present study determines whether cultured human VSMCs express mRNA for VPF and whether VPF mRNA expression is influenced by human VSMC proliferation. 2. A 204 bp cDNA fragment, specific for all known variants of VPF mRNA, was cloned and used to demonstrate that human VSMCs express abundant quantities of VPF mRNA, whereas human endothelial cells do not. VPF mRNA levels were markedly diminished in non-proliferating human VSMCs. In contrast, when human VSMCs were stimulated to proliferate by exposure to serum, there was a rapid 6.6-fold increase (P < 0.01 versus time 0 h) in VPF mRNA expression, which was maximal at 3 h and persisted beyond 24 h. The magnitude of the VPF mRNA response in human VSMCs was dependent on the serum concentration. 3. Platelet-derived growth factor also increased VPF mRNA expression by human VSMCs, thus confirming that recognized growth factors for VSMCs also potently influence the VPF gene. 4. In conclusion, VPF mRNA is expressed by human VSMCs, the magnitude of VPF expression being temporally related to the proliferation of human VSMCs and the potency of the growth-promoting stimulus. We propose that VPF produced by proliferating human VSMCs could act as a paracrine hormone to powerfully influence the permeability and growth of the overlying vascular endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of peritoneal dissemination of ovarian cancer by tyrosine kinase receptor inhibitor SU6668 (TSU‐68)

“…21 Both PDGF and bFGF are involved in tumor proliferation 22,23 and induce VEGF. 24,25 PDGF is a pericyte mitogen that plays an important role in the regulation of angiogenesis, 26 -28 and is also reported to be a permeabilizing agent. 29 SU6668 is an inhibitor of the tyrosine kinase receptors for the above-described 3 angiogenesis factors, and is characterized by its broad spectrum of action.…”

Putative pathophysiological role of growth factors and cytokines in experimental diabetic kidney disease

“…In addition, phorbol esters stimulate mesangial VEGF production [139] and notably, inhibition of PKC blocks VEGF signalling [140]. Further, various growth factors and cytokines, including TGF-b [141,142], IGF-I [143], basic fibroblastic growth factor (bFGF) [144] and platelet derived growth factor (PDGF) [136,145] have been shown to stimulate VEGF production in various non-renal cell types. Finally, as mentioned above, both IGF-I [79] and VEGF [80] stimulate NF-kB concentrations in endothelial cells in vitro.…”

Elevated Circulating Levels of Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor in Patients With Acute Myocardial Infarction

“…ecently there has been marked progress in the study of growth factors and of these, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are known for their widespread distribution in vivo, [1][2][3] as well as their strong angiogenetic effect in ischemic animal models. [4][5][6][7] Recent experimental studies have demonstrated that exogenously administered bFGF and VEGF augmented collateral vessel development in animal models of hindlimb ischemia, 4,5 and they also showed an effect in reducing the infarcted myocardium in canine coronary occlusion.…”