Sgadari Cecilia, Barillari Giovanni, Palladino Clelia, Bellino Stefania, Taddeo Brunella, Toschi Elena, Ensoli Barbara
National AIDS Center, Istituto Superiore di Sanità, 00161 Rome, Italy.
Int J Vasc Med. 2011;2011:452729. doi: 10.1155/2011/452729. Epub 2011 Oct 9.
Kaposi's sarcoma (KS) is a vascular tumor frequently occurring in Human Immunodeficiency Virus- (HIV-) 1-infected individuals. Our previous work indicated that the angiogenic fibroblast growth factor (FGF)-2 and the Tat protein of HIV-1, both expressed in KS lesions of HIV-infected patients, synergize at inducing angioproliferative, KS-like lesions in mice. Here we show that the development of angioproliferative lesions promoted in mice by combined Tat and FGF-2 associates with an increase in the levels of expression of the antiapoptotic Bcl-2 protein. Upregulation of Bcl-2 expression by combined FGF-2 and Tat occurs also in vitro, and this protects human primary endothelial cells from programmed cell death. As Bcl-2 is expressed in human KS lesions in a fashion paralleling the progression of the disease, these findings suggest a molecular mechanism by which Tat and FGF-2 cooperate in KS maintenance and progression in HIV-infected individuals.
卡波西肉瘤（KS）是一种常见于人类免疫缺陷病毒1型（HIV-1）感染者的血管性肿瘤。我们之前的研究表明，血管生成性成纤维细胞生长因子（FGF）-2和HIV-1的Tat蛋白在HIV感染患者的KS病变中均有表达，二者协同作用可在小鼠体内诱导血管增生性、类似KS的病变。在此我们表明，联合Tat和FGF-2在小鼠体内促进血管增生性病变的发生与抗凋亡Bcl-2蛋白表达水平的升高相关。FGF-2和Tat联合作用也会在体外上调Bcl-2的表达，这可保护人原代内皮细胞免于程序性细胞死亡。由于Bcl-2在人类KS病变中的表达方式与疾病进展平行，这些发现提示了一种分子机制，通过该机制Tat和FGF-2在HIV感染个体的KS维持和进展过程中发挥协同作用。
