Rega G, Kaun C, Demyanets S, Pfaffenberger S, Rychli K, Hohensinner P J, Kastl S P, Speidl W S, Weiss T W, Breuss J M, Furnkranz A, Uhrin P, Zaujec J, Zilberfarb V, Frey M, Roehle R, Maurer G, Huber K, Wojta J
Department of Internal Medicine II, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Arterioscler Thromb Vasc Biol. 2007 Jul;27(7):1587-95. doi: 10.1161/ATVBAHA.107.143081. Epub 2007 May 24.
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.
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-1beta 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.
We speculate that the inflammatory cytokines IL-6 and OSM might support angiogenesis during adipose tissue growth by upregulating VEGF.
人们认为脂肪组织作为一个内分泌器官，通过产生炎症介质，从而导致肥胖人群心血管疾病风险增加。脂肪组织量与血管生成之间的联系已被提出。血管内皮生长因子（VEGF）似乎参与了这一过程。糖蛋白（gp）130配体家族成员可调节其他细胞中的VEGF表达。
我们使用组织外植体以及来自人类皮下和内脏脂肪组织的前脂肪细胞和脂肪细胞原代培养物，来研究gp130配体抑瘤素M（OSM）、白细胞介素-6（IL-6）、白血病抑制因子（LIF）和心肌营养素-1（CT-1）是否调节人类脂肪组织中的VEGF表达。人类皮下和内脏脂肪组织对IL-6和OSM治疗有反应，VEGF产生显著增加。从皮下和内脏脂肪组织中分离出人类前脂肪细胞。通过补充激素诱导脂肪细胞分化。所有细胞类型对IL-6和OSM均有反应，VEGF蛋白产生显著增加，VEGF特异性mRNA也有类似增加。此外，IL-1β协同增强了OSM对VEGF产生的作用。JAK/STAT抑制剂AG-490几乎完全消除了OSM依赖的VEGF诱导。在小鼠中，IL-6和OSM增加了血清VEGF水平、VEGF mRNA以及脂肪组织中的血管密度。
我们推测炎症细胞因子IL-6和OSM可能通过上调VEGF来支持脂肪组织生长过程中的血管生成。
