Subcutaneous adipocyte apoptosis in HIV-1 protease inhibitor-associated lipodystrophy
Subcutaneous adipocyte apoptosis in HIV-1 protease inhibitor-associated lipodystrophy
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DOI：
10.1097/00002030-199911120-00008
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发表时间：
1999-11-12
期刊：
影响因子：
3.8
通讯作者：
Vázquez, G
中科院分区：
文献类型：
--
作者：
Domingo, P;Matias-Guiu, X;Vázquez, G
背景：HIV-1蛋白水解酶抑制剂可引起血浆中HIV-1RNA的迅速下降，并伴随着免疫重建。然而，严重的代谢副作用以及一种以前未见过的脂肪营养不良与长期使用蛋白酶抑制剂治疗有关。HIV-1蛋白水解酶抑制物相关性脂肪营养不良的发病机制尚不清楚。方法：对14例HIV感染的HIV-1蛋白水解酶抑制物相关脂营养不良患者进行了右腿前外侧皮下脂肪活检。这些样本被提交进行标准的病理学研究，同时仔细寻找脂肪细胞的凋亡。用脱氧核糖核酸末端转移酶dUTP-地高辛缺口末端标记法(TUNEL)检测细胞的凋亡，使用美国马里兰州盖瑟斯堡Oncor试剂盒。对每个样本进行了三到五次的程序。采用适当的阳性对照和阴性对照。结果：14例HIV感染者，平均暴露于HIV-1蛋白酶抑制剂的时间为12.6+/-3.7个月(范围：6-21个月)，出现了HIV-1蛋白酶抑制剂相关性脂肪营养不良的特征。除了一名患者外，所有患者都有异常的腰臀比，而且他们都表现出异常的血脂谱。病理上，皮下脂肪萎缩是一个恒定的特征，伴随着局限性脂肪肉芽肿的形成和血管的增殖。在11个可评估的活检样本中，1个为阴性，6个为局灶性阳性的凋亡细胞，其余4个活检为中等阳性。在内皮细胞中也检测到了细胞凋亡的变化。结论：HIV-1蛋白水解酶抑制物相关性脂肪营养不良患者皮下脂肪细胞发生凋亡。(C)1999年，Lippincott Williams&Wilkins。
Background: Inhibitors of HIV-1 protease produce a rapid decrease in plasma HIV-1 RNA, with concomitant immune reconstitution. However, severe metabolic side effects together with a previously unseen form of lipodystrophy have been associated with long-term use of protease-inhibitor therapy. The pathogenic mechanisms underlying HIV-1 protease inhibitor-associated lipodystrophy are still largely unknown.Methods: Fourteen HIV-infected patients with HIV-1 protease inhibitor-associated lipodystrophy had a biopsy of subcutaneous fat performed in the antero-lateral aspect of the right leg. The samples were submitted for standard pathologic study together with a careful search for adipocyte apoptosis. Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP-digoxigenin nick end labelling (TUNEL) method, using the ApopTag kit (Oncor, Gaithersburg, Maryland, USA). The procedure was performed between three and five times for each sample. Appropriate positive and negative controls were used. Controls which were subcutaneous fat biopsies from patients with untreated melanoma were also examined for the presence of apoptosis.Results: Fourteen HIV-infected patients with a mean exposure to HIV-1 protease inhibitors of 12.6 +/- 3.7 months (range: 6-21 months), developed the characteristic features of HIV-1 protease inhibitor-associated lipodystrophy. All but one patient had an abnormal waist:hip ratio, and they all exhibited an abnormal serum lipid profile. Pathologically, subcutaneous fat atrophy was a constant feature, along with focal lipogranuloma formation and vascular proliferation. One of the eleven assessable biopsy samples was negative for the presence of apoptosis, six showed focally positive apoptotic cells, and the remaining four biopsies demonstrated moderate positivity. Apoptotic changes were also detected in endothelial cells. Apoptotic changes were more pronounced in patients with higher increases in CD4 and CD8 counts, and in those with a greater decay in plasma viral load.Conclusions: Subcutaneous adipocyte apoptosis occurs in lipoatrophic areas of patients with HIV-1 protease inhibitor-associated lipodystrophy. (C) 1999 Lippincott Williams & Wilkins.