Endothelial Cells Synthesize Basic Fibroblast Growth Factor and Transforming Growth Factor Beta

Abstract

Endothelial cells, including human umbilical vein endothelial cells (HUVEC), bovine aortic endothelial cells (BAEC), and bovine capillary endothelial cells (BCEC) in culture synthesize basic fibroblast growth factor (bFGF) and transforming growth factor type beta (TGF-beta). Basic FGF was cell-associated and synthesis was demonstrated by (i) the presence of bFGF mRNA species, (ii) binding to heparin-Sepharose and elution at 1.5 M NaCl, (iii) cross-reactivity with anti-bFGF antibodies when analyzed by electrophoretic blotting, and (iv) biological activity. Basic FGF was found in cell lysates at 2.3 ng/10(6) cells in HUVEC, 2.0 ng/10(6) cells in BCEC, and 13 ng/10(6) cells in BAEC. TGF-beta was secreted into media, and synthesis was demonstrated by (i) presence of TGF-beta mRNA species, (ii) cross-reactivity with anti-TGF-beta antibodies when analyzed by immunoprecipitation, (iii) competitive binding with authentic human platelet-derived TGF-beta that was blocked by TGF-beta specific blocking antibodies, and (iv) inhibition of [3H]TdR incorporation in CCl-64 cells. TGF-beta was secreted in an inactive form and required acid activation for detection. HUVEC synthesized 2.0 ng TGF-beta/10(6) cells per 12 hr; BCEC, 3.5 ng; and BAEC, 3.5 ng. HUVEC proliferation was not affected by treatment with exogenous TGF-beta, while BCEC proliferation was decreased by treatment with TGF-beta. Vascular endothelium is thus a source for these two potent multifunctional regulatory molecules, both of which may affect the growth of endothelium and neighboring fibroblasts, smooth muscle cells and white blood cells. The activation or release of these factors by endothelium may be a precipitating event in important cellular processes such as wound healing, organogenesis, and angiogenesis.

Proliferation and differentiation of smooth muscle cell precursors occurs simultaneously during the development of the vessel wall

“…The mechanisms that regulate SMC modulation to the synthetic and proliferative state has been the focus of several laboratories. Research in this area revealed that a number of cytokines are involved in this transition, including PDGF and TGF-b (Collins et al, 1987;Hannan et al, 1988;Sato et al, 1990;Ross et al, 1993). Nevertheless, it appears certain that multiplicity of molecular pathways are involved in pathological SMC replication associated with arterial lesions.…”

“…Therefore, it is reasonable to suggest that the endothelium might be used as a template for recruitment and migration of presumptive SMCs and perhaps might regulate this process. Heparin-like molecules Fritze et al, 1985;Castellot et al, 1982) and several growth factors such as PDGF, bFGF, and TGFb are secreted by the endothelium (Collins et al, 1987;Hannan et al, 1988;Sato et al, 1990). These and other factors may play a role in recruitment and migration of undifferentiated SMC precursors in vivo.…”

Transforming growth factor-beta activity in sheep lung lymph during the development of pulmonary hypertension.

“…While it is possible that the airway cells contribute to the level of TGF-# in lung lymph, the level is tenfold greater than that found in epithelial lining fluid, suggesting that TGF-# is also produced by other cells in the interstitium and/or vascular wall. Endothelial cells (30) and lymphocytes (31,32) have been reported to produce TGF-# in vitro and may also contribute to the TGF-4 in lung lymph.…”

Endothelial Regulation of Vascular Tone and Growth

“…51 Important growth inhibitors produced by the endothelium are heparin, heparin sulfates, transforming growth factor-β, and most likely nitric oxide. 52,53 On the other hand, endo thelial cells can also produce growth factors such as basic fibroblast growth factor, platelet-derived growth factor (PDGF), and possibly also endothelin ( Figure 6). 54,55 These factors contribute to proliferative re sponses, at least under certain conditions, whereas it has to be assumed that under normal conditions inhib itory stimuli prevail.…”