Kanmogne Georgette D, Primeaux Charles, Grammas Paula
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Biochem Biophys Res Commun. 2005 Aug 12;333(4):1107-15. doi: 10.1016/j.bbrc.2005.05.198.
Pulmonary hypertension associated with human immunodeficiency virus (HIV) infection also involves injury to the lung endothelium. However, the pathogenesis of HIV-induced pulmonary hypertension is not known; we hypothesized that HIV or secreted viral proteins could play a role in vascular injury and the increased frequency of pulmonary hypertension observed in HIV-infected patients. Here, we report that exposure of HIV-1 gp120 proteins to primary human lung microvascular endothelial cells causes apoptosis, as assessed by TUNEL assay, Annexin-V staining, and DNA laddering. Using ribonuclease protection assay and Western blotting we find that gp120-induced apoptosis of lung endothelial cells involves a down-regulation in Bcl-xl mRNA and proteins. In addition, gp120 significantly increases secretion of the potent vasoconstrictor endothelin-1 by human lung endothelial cells. These data suggest that secreted HIV gp120 proteins induce lung endothelial cell injury and could contribute to the development of HIV-associated pulmonary hypertension.
与人类免疫缺陷病毒（HIV）感染相关的肺动脉高压也涉及肺内皮损伤。然而，HIV诱导的肺动脉高压的发病机制尚不清楚；我们推测HIV或分泌的病毒蛋白可能在血管损伤以及在HIV感染患者中观察到的肺动脉高压频率增加中起作用。在此，我们报告，通过TUNEL检测、膜联蛋白V染色和DNA梯状条带分析评估，HIV-1 gp120蛋白作用于原代人肺微血管内皮细胞会导致细胞凋亡。使用核糖核酸酶保护分析和蛋白质印迹法，我们发现gp120诱导的肺内皮细胞凋亡涉及Bcl-xl mRNA和蛋白质的下调。此外，gp120显著增加人肺内皮细胞分泌强效血管收缩剂内皮素-1。这些数据表明，分泌的HIV gp120蛋白可诱导肺内皮细胞损伤，并可能促成HIV相关肺动脉高压的发展。
