Human immunodeficiency virus transgenic rats exhibit pulmonary hypertension.
Human immunodeficiency virus transgenic rats exhibit pulmonary hypertension.
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人类免疫缺陷病毒转基因大鼠表现出肺动脉高压。
DOI：
10.1152/ajplung.00045.2011
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Naik,JayS
中科院分区：
文献类型：
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作者：
Lund,AmieK;Lucero,Joann;Herbert,Lindsay;Liu,Yushi;Naik,JayS
人类免疫缺陷病毒(HIV)相关性肺动脉高压(PAH)是一种严重的非传染性疾病，涉及肺血管压力的异常升高，导致右室(RV)心力衰竭，最终可导致死亡。由于缺乏可行的HIV-PAH动物模型，限制了对参与HIV介导的PAH发生和发展的信号通路的识别。为了确定HIV-1转基因(HIV TG)大鼠是否表现出与PAH相关的病理生理终点，我们通过实时荧光定量PCR和基因芯片检测了RV峰值收缩压(RVSP)、RV肥厚、肺血管重构和基因表达的变化。在2%异氟醚麻醉下，3个月龄和9个月龄HIV TG和年龄匹配的Fischer 344(对照组)雄性大鼠右颈静脉插管测定RVSP。HIVTG组RVSP升高(34.2±2.5)mm Hg，F344对照组RVSP升高(21.2±2.5)mm Hg，9个月龄HIVTg组RVSP升高(42.5±3.7)mm Hg。通过组织学和超声心动图测量，我们观察到HIV TG组大鼠右室壁厚度与对照组相比显著增加。HIVTG大鼠还表现出肺动脉增厚和小肺动脉重塑，以及与PAH相关的基因通路的表达改变。这些数据代表了对HIV TG大鼠的PAH的第一次分析，并表明该模型将有助于研究HIV-PAH的途径和确定潜在的治疗方法。
Human immunodeficiency virus (HIV)-associated pulmonary arterial hypertension (PAH) is a serious noninfectious disease involving an aberrant increase in pressure in the blood vessels of the lung, which leads to right ventricular (RV) heart failure and can eventually result in death. A lack of viable animal models of HIV-PAH has limited the identification of signaling pathways involved in HIV-mediated onset and progression of PAH. To determine whether the HIV-1 transgenic (HIV Tg) rat displays pathophysiological end points associated with PAH, we evaluated peak RV systolic pressure (RVSP), RV hypertrophy, pulmonary vessel remodeling, and alterations in gene expression by real-time PCR and microarray. RVSP was measured by RV catheterization via the right jugular vein in 3- and 9-mo-old HIV Tg and age-matched Fischer 344 (control) male rats while under 2% isoflurane anesthesia. RVSP was elevated in the HIV Tg rats (34.2 ± 2.5 mmHg) compared with the F344 controls (21.2 ± 2.5 mmHg), with more significant elevations in the 9-mo-old HIV Tg rats (42.5 ± 3.7 mmHg). We observed significant increases in RV wall thickness in HIV Tg rats compared with controls, both histologically and by echocardiograph measurement. HIV Tg rats also show increased thickening of the pulmonary artery and remodeling of small pulmonary arteries, as well as altered expression of gene pathways associated with PAH. These data represent the first analysis of PAH in HIV Tg rats and suggest that this model will be useful for investigating pathways and identifying potential therapies for HIV-PAH.