HAART drugs induce mitochondrial damage and intercellular gaps and gp120 causes apoptosis.
HAART drugs induce mitochondrial damage and intercellular gaps and gp120 causes apoptosis.
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DOI：
10.1385/ct:4:4:327
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发表时间：
2004-01-01
影响因子：
3.2
通讯作者：
Arthos, James
中科院分区：
文献类型：
--
作者：
Fiala, Milan;Murphy, Thomas;Arthos, James
HIV-1感染与严重的心血管并发症有关，但HIV-1、病毒蛋白和高效抗逆转录病毒治疗(HAART)药物的作用尚不清楚。HAART降低了心脏病的总体风险，但会导致代谢紊乱，可能还会导致冠状动脉疾病。我们研究了HIV-1、HIV-1糖蛋白120(Gp120)和HAART药物对人冠状动脉内皮细胞(CAECs)、脑微血管内皮细胞和新生大鼠心室肌细胞(NRVMs)的毒性。HIV-1和gp120可诱导NRVMs和CAECs的凋亡，而叠氮胸苷(AZT)无此作用。一氧化氮合酶抑制剂乙基异硫脲可抑制gp120诱导的细胞凋亡。AZT、HIV-1和gp120均损伤心肌细胞线粒体。HAART药物、AZT和Indinavir，而不是HIV-1，会在融合的内皮细胞之间产生细胞间隙，并降低跨内皮电阻。综上所述，HIV-1和gp120通过诱导心肌细胞和内皮细胞凋亡而产生毒性作用。HAART药物破坏内皮细胞连接和线粒体，并可能导致血管损伤。
HIV-1 infection is associated with serious cardiovascular complications, but the roles of HIV-1, viral proteins, and highly active antiretroviral therapy (HAART) drugs are not understood. HAART decreases the overall risk of heart disease but leads to metabolic disturbances and possibly coronary artery disease. We investigated toxicities of HIV-1, HIV-1 glycoprotein 120 (gp120), and HAART drugs for human coronary artery endothelial cells (CAECs), brain microvascular endothelial cells, and neonatal rat ventricular myocytes (NRVMs). HIV-1 and gp120, but not azidothymidine (AZT), induced apoptosis of NRVMs and CAECs. Ethylisothiourea, an inhibitor of nitric oxide synthase, inhibited apoptosis induction by gp120. AZT, HIV-1, and gp120 all damaged mitochondria of cardiomyocytes. HAART drugs, AZT, and indinavir, but not HIV-1, produced intercellular gaps between confluent endothelial cells and decreased transendothelial electrical resistance. In conclusion, HIV-1 and gp120 induce toxicity through induction of cardiomyocyte and endothelial cell apoptosis. HAART drugs disrupt endothelial cell junctions and mitochondria and could cause vascular damage.