Vascular Endothelial Growth Factor Is the Major Angiogenic Factor in Omentum: Mechanism of the Omentum-Mediated Angiogenesis

Abstract

These data suggest that VEGF is the major angiogenic Omentum has been used clinically to promote wound factor produced by omentum and possibly underlies healing and to stimulate the revascularization of ischthe mechanism of omentum-induced angiogenesis.emic tissues.The biologic mechanism responsible for Augmented expression of VEGF by omental cells under these effects has, however, not yet been defined.A hypoxic conditions may furthermore reflect the mechnumber of polypeptide growth factors that possess poanism responsible for enhancing the angiogenic activtent angiogenic properties have recently been identiity of omentum in the setting of ischemia.᭧ 1997 Academic fied, and we therefore sought to determine whether Press one of these growth factors might be responsible for the angiogenic properties of the omentum.The levels of vascular endothelial growth factor (VEGF) protein INTRODUCTION in a number of rat tissues and organs were analyzed by Western and enzyme immunoassay analysis.Because Angiogenesis, the formation of new capillaries and omentum was found to have the greatest VEGF conblood vessels, plays a key role in normal physiological centrations of the tissues examined, antibody neutralprocesses such as growth and wound healing and in ization, transcription inhibition assays, and Northern the progression of pathological conditions such as tublot analysis were performed under hypoxic and normorogenesis and atherosclerosis [1].The angiogenic moxic conditions on tissue extractions and primary tissue cultures of omentum to further characterize the processes are thought to be regulated by a balance befunctional significance of VEGF expression in these tween stimulatory angiogenic factors, including fibrotissues.The omentum demonstrated the highest VEGF blast growth factor (FGF), platelet-derived growth facsecretion rate as well as the highest concentration of tor, and vascular endothelial growth factor (VEGF), VEGF protein of the various rat tissues and organs and inhibitory angiogenic factors such as angiostatic examined.Fractionation studies of the omentum fursteroids and angiostatin [2].thermore demonstrated that omental adipocytes, The angiogenic property of omentum has been docurather than the stromal-vascular cells, were the primented since 1585.Ever since these initial observamary source of VEGF protein.An endothelial cell mitotions, omentum has been used clinically to promote genic assay showed that a major portion of the mitorevascularization and healing of compromised or ischgenic activity of heparin-binding proteins and condiemic organs and tissues, including the myocardium tioned media derived from omentum was abolished by and intestinal and bronchial anastomoses [3-5].The VEGF antibody.Additional studies with the transcripimproved healing induced by omentum has been demtion inhibitor actinomycin-D furthermore demononstrated to be the result of new blood vessel formation, strated that the VEGF gene was continuously tranor angiogenesis.Despite these clinical applications, the scribed in the rat omental adipocytes.Incubation of angiogenic factor(s) in omentum has not yet been identhe omental adipocytes under hypoxic conditions intified.duced approximately a 1.7-fold increase in VEGF pro-Adipose tissue including the omentum, once contein expression, which was abolished by actinomycinceived of as a relatively inactive biological substrate, D. Northern blot analysis demonstrated that hypoxia in fact serves as the primary site for a number of critical resulted in upregulation of the VEGF mRNA in the biologic functions including fatty acid metabolism and hypoxia-cultured omental adipocytes, suggesting that lipoprotein lipase synthesis [6].Adipose tissue is also the augmentation of VEGF expression in omental adipocytes by hypoxia occurs at the transcriptional level.capable of producing and secreting substances such as adipsin and tumor necrosis factor-a that have significant regulatory functions [7].Because adipose tissue 1 Supported in part by an American Heart Association Grant-in-Aid (94066).serves as an important conduit for the vasculature, it