Grainger David J
Department of Medicine, University of Cambridge, Box 157, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK.
Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):399-404. doi: 10.1161/01.ATV.0000114567.76772.33. Epub 2003 Dec 29.
The role of the anti-inflammatory cytokine transforming growth factor beta (TGF-beta) in atherosclerosis has been the subject of considerable debate for a decade. In the early 1990s, we postulated that TGF-beta played an important role in maintaining normal vessel wall structure and that loss of this protective effect contributed to the development of atherosclerosis. We termed this the protective cytokine hypothesis. This proposal was slow to gain broad acceptance, however, because at that time there were little data available on the role of TGF-beta during the development of atherosclerosis but much information about its role during trauma-induced neointima formation. Because TGF-beta apparently aggravates neointima formation, both by inhibiting endothelial regeneration and by promoting fibrosis, it was difficult to accept that its presence might ameliorate the superficially similar atherogenesis process. But several recent studies revealed beyond doubt the fact that TGF-beta protects against lipid lesion formation, at least in mouse models of atherosclerosis. Therefore, two important questions remain. First, is the role of TGF-beta in vascular biology similar in humans and in mice? Secondly, how important, compared with defects in thrombosis or lipoprotein metabolism, is the protective role of TGF-beta during atherogenesis?
十年来，抗炎细胞因子转化生长因子β（TGF-β）在动脉粥样硬化中的作用一直是激烈争论的焦点。20世纪90年代初，我们推测TGF-β在维持正常血管壁结构方面发挥着重要作用，而这种保护作用的丧失会促使动脉粥样硬化的发展。我们将此称为保护性细胞因子假说。然而，这一观点在当时并未迅速得到广泛认可，因为那时关于TGF-β在动脉粥样硬化发展过程中的作用的数据很少，而关于其在创伤诱导的新生内膜形成过程中的作用却有很多信息。由于TGF-β明显会通过抑制内皮再生和促进纤维化来加重新生内膜形成，所以很难接受它的存在可能会改善表面上与之相似的动脉粥样硬化形成过程。但最近的几项研究毫无疑问地揭示了这样一个事实，即TGF-β至少在动脉粥样硬化的小鼠模型中能预防脂质病变的形成。因此，仍存在两个重要问题。第一，TGF-β在人类和小鼠血管生物学中的作用是否相似？第二，与血栓形成或脂蛋白代谢缺陷相比，TGF-β在动脉粥样硬化形成过程中的保护作用有多重要？
