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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1587.)
© 2007 American Heart Association, Inc.

Vascular Biology

Vascular Endothelial Growth Factor Is Induced by the Inflammatory Cytokines Interleukin-6 and Oncostatin M in Human Adipose Tissue In Vitro and in Murine Adipose Tissue In Vivo

G. Rega; C. Kaun; S. Demyanets; S. Pfaffenberger; K. Rychli; P.J. Hohensinner; S.P. Kastl; W.S. Speidl; T.W. Weiss; J.M. Breuss; A. Furnkranz; P. Uhrin; J. Zaujec; V. Zilberfarb; M. Frey; R. Roehle; G. Maurer; K. Huber; J. Wojta

From the Departments of Internal Medicine II (G.R., C.K., S.D., S.P., K.R., P.J.H., S.P.K., W.S.S., T.W.W., G.M., J.W.) and Surgery (M.F.), Medical University Vienna; Ludwig Boltzmann Cluster for Cardiovascular Research (S.P.K., J.W.), Vienna; the Department of Vascular Biology and Thrombosis Research (J.M.B., P.U., J.Z.), Medical University Vienna; and the 2nd Department of Surgery (R.R.) and the 3rd Medical Department for Cardiology and Emergency Medicine (A.F., K.H.), Wilhelminenhospital, Vienna, Austria; and the Department of Cell Biology (V.Z.), Institute Cochin, Paris, France.

Correspondence to Johann Wojta, Department of Internal Medicine II, Medical University Vienna, Waehringer Guertel 18–20, A-1090 Vienna, Austria. E-mail johann.wojta{at}meduniwien.ac.at

Objectives— It is believed that adipose tissue acts as an endocrine organ by producing inflammatory mediators and thereby contributes to the increased cardiovascular risk seen in obesity. A link between adipose tissue mass and angiogenesis has been suggested. Vascular endothelial growth factor (VEGF) seems to be implicated in this process. Members of the glycoprotein (gp)130 ligand family regulate VEGF expression in other cells.

Methods and Results— We used tissue explants as well as primary cultures of preadipocytes and adipocytes from human subcutaneous and visceral adipose tissue to investigate whether the gp130 ligands oncostatin M (OSM), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and cardiotrophin-1 (CT-1) regulate VEGF expression in human adipose tissue. Human subcutaneous and visceral adipose tissue responded to treatment with IL-6 and OSM with a significant increase in VEGF production. Human preadipocytes were isolated from subcutaneous and visceral adipose tissue. Adipocyte-differentiation was induced by hormone-supplementation. All cell types responded to IL-6 and OSM with a robust increase in VEGF protein production and a similar increase in VEGF-specific mRNA. Furthermore, IL-1ß synergistically enhanced the effect of OSM on VEGF production. AG-490, a JAK/STAT inhibitor, abolished the OSM-dependent VEGF induction almost completely. In mice, IL-6 and OSM increased serum levels of VEGF and VEGF mRNA and vessel density in adipose tissue.

Conclusion— We speculate that the inflammatory cytokines IL-6 and OSM might support angiogenesis during adipose tissue growth by upregulating VEGF.

Recent studies found that adipose tissue mass could be regulated through the vasculature. We show that the inflammatory cytokines IL-6 and OSM upregulate VEGF in human adipose tissue via JAK/STAT. We hypothesize that a link between adipokines, vascularization, adipose tissue growth, and thus possibly also cardiovascular diseases could exist.

Key Words: obesity • angiogenesis • inflammation • cytokines

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