Aortic endothelial cells synthesize basic fibroblast growth factor which remains cell associated and platelet‐derived growth factor‐like protein which is secreted

Abstract

Cultured bovine aortic endothelial cells synthesize growth factors which markedly differ in the regulation of their storage and secretion. Endothelial cell lysates, but not conditioned medium, contain a growth factor activity that appears to be basic fibroblast growth factor (FGF) by the following criteria: (1) it elutes from heparin-Sepharose at 1.4-1.6 M NaCl; (2) it is mitogenic for bovine aortic and capillary endothelial cells; (3) it is heat sensitive but stable to dithiothreitol; (4) it has a molecular weight of about 18,000 daltons; and (5) it cross-reacts with antiserum directed against basic FGF. In contrast, endothelial cell conditioned medium, but not lysates, contains a growth factor activity that (1) elutes from heparin-Sepharose at 0.4-0.5 M NaCl; (2) is mitogenic for fibroblasts and vascular smooth muscle cells but not for capillary endothelial cells; (3) is heat stable and dithiothreitol sensitive; and (4) competes with platelet-derived growth factor (PDGF) for binding to fibroblasts. From these criteria, it appears that endothelial cells secrete into the medium growth factors some of which are PDGF-like, but secrete little if any basic FGF. It is suggested that endothelial cell-associated basic FGF acts in an autocrine fashion to stimulate endothelial cell proliferation in response to endothelial cell perturbation or injury. On the other hand, the endothelial cell-secreted growth factors which are smooth muscle cell but not endothelial cell mitogens might exert a paracrine function on neighboring cells of the vessel wall.

Polymorphonuclear leukocytes enhance release of growth factors by cultured endothelial cells.

“…Endothelial cells in vitro synthesize polypeptide growth factors, collectively named endothelium-derived growth factors (EDGFs), including basic fibroblast growth factor (bFGF) 5 - 7 and a platelet-derived growth factor (PDGF)-like molecule. 5 - 8 Enhanced secretion of EDGFs has been found after stimulation of cultured endothelial cells with agonists such as thrombin, 9 factor Xa, 10 low-molecular-weight fibrinogen degradation products, 11 bacterial endotoxin, 12 and tumor necrosis factor.…”

“…5 - 8 Enhanced secretion of EDGFs has been found after stimulation of cultured endothelial cells with agonists such as thrombin, 9 factor Xa, 10 low-molecular-weight fibrinogen degradation products, 11 bacterial endotoxin, 12 and tumor necrosis factor. 13 Received January 19,1993; revision accepted October 17, 1993.…”

“…- 27 Endothelial cells synthesize PDGF, which has been shown to be secreted into the surrounding medium, 5 -8 ' 24 and bFGF, which has been reported to remain cell associated 5 or deposited in the extracellular matrix. 38 In the present study the enhancement in EDGF release was measured both when cells retracted and when cells retained the normal cobblestone morphology.…”

Fluid shear stress differentially modulates expression of genes encoding basic fibroblast growth factor and platelet-derived growth factor B chain in vascular endothelium.

“…We chose to investigate the effect of fluid shear stress applied in vitro to confluent monolayers of BAE cells on the mRNA expression of basic fibroblast growth factor (bFGF) and platelet-derived growth factor B-chain (PDGF-B). bFGF and PDGF-B are potent heparin-binding polypeptide growth factors (22) with important chemotactic and mitogenic properties that have been proposed as key players in determining vascular structural response in models of injury (23) and atherosclerosis (24,25). bFGF is mitogenic to endothelial and smooth muscle cells, and is a powerful angiogenic factor that is associated with the extracellular matrix and basement membrane (26).…”

Basic fibroblast growth factor enhances the coupling of intimal hyperplasia and proliferation of vasa vasorum in injured rat arteries.

“…Accelerated atherosclerosis is increasingly being recognized as an important rate limiting factor in angioplasty, vascular bypass surgery and organ transplantation (1,2). We have focused on two aspects of this phenomenon; the neointimal proliferation of smooth muscle cells factor (bFGF)' is synthesized by endothelial cells (16,17), mac-rophages, and SMCs (18) and is mitogenic for endothelial cells and SMCs (19)(20)(21), and angiogenic (19,(22)(23)(24)(25). It is associated with the extracellular matrix and basement membrane (26)(27)(28)(29).…”