Gutierrez Jose, Menshawy Khaled, Gonzalez Marco, Goldman James, Elkind Mitchell S V, Marshall Randolph, Morgello Susan
aDepartment of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, USAbAlexandria Faculty of Medicine, EgyptcDepartment of Neurological Sciences, University of Nebraska Medical Center, NebraskadDepartment of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University Medical CentereDepartment of Epidemiology, Mailman School of Public Health, Columbia University Medical CenterfDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, USA.
AIDS. 2016 Jan 28;30(3):415-23. doi: 10.1097/QAD.0000000000000927.
To test the hypothesis that brain arteries from HIV+ cases have a greater degree of inflammation than brain arteries from HIV- cases, and that inflammation is associated with brain arterial remodeling.
Case-control study, cross-sectional.
Brain arteries from 162 autopsy cases (84 with HIV) were systematically analyzed for thickness of the intima, media, and adventitia, and atherosclerosis and dolichoectasia. Inflammation was assessed with CD68 immunohistochemistry, and measured with a semiquantitative score reflecting the number and location (i.e., arterial layer) of activated macrophages infiltrating the arterial wall. Latent varicella zoster virus (VZV) was assessed with anti-VZV gene 63 product immunohistochemistry. Demographic and clinical variables were available in all cases, and longitudinal data about CD4 cell counts were available among cases with HIV. Multilevel generalized linear models were used to test the association between inflammation and HIV.
Arteries from HIV+ cases had a higher inflammation score (B = 0.36, P = 0.05) compared with arteries from HIV- cases, although the association was attenuated after controlling for demographic variables, vascular risk factors, and latent VZV (B = 0.20, P = 0.18). Although intimal inflammation was similar in cases with and without HIV, adventitial inflammation was associated with HIV. Intimal inflammation was associated with intracranial atherosclerosis independent of HIV status, but adventitial inflammation was associated with HIV-associated dolichoectasia in arteries with a thin media.
Adventitial inflammation is associated with HIV and dolichoectasia independent of intracranial atherosclerosis. This suggests that differential inflammatory responses may play a role in intracranial atherosclerosis and dolichoectasia.
检验以下假设:与未感染HIV的病例的脑动脉相比,感染HIV病例的脑动脉炎症程度更高,且炎症与脑动脉重塑相关。
病例对照横断面研究。
对162例尸检病例(84例感染HIV)的脑动脉进行系统分析,测量内膜、中膜和外膜厚度,以及动脉粥样硬化和动脉扩张情况。采用CD68免疫组织化学法评估炎症,并通过反映浸润动脉壁的活化巨噬细胞数量和位置(即动脉层)的半定量评分进行测量。采用抗水痘带状疱疹病毒(VZV)基因63产物免疫组织化学法评估潜伏性VZV。所有病例均有人口统计学和临床变量数据,感染HIV的病例有CD4细胞计数的纵向数据。采用多水平广义线性模型检验炎症与HIV之间的关联。
与未感染HIV的病例的动脉相比,感染HIV病例的动脉炎症评分更高(B = 0.36,P = 0.05),但在控制人口统计学变量、血管危险因素和潜伏性VZV后,这种关联减弱(B = 0.20,P = 0.18)。尽管感染和未感染HIV的病例内膜炎症相似,但外膜炎症与HIV相关。内膜炎症与颅内动脉粥样硬化相关,与HIV状态无关,但外膜炎症与中膜薄的动脉中与HIV相关的动脉扩张相关。
外膜炎症与HIV及动脉扩张相关,与颅内动脉粥样硬化无关。这表明不同的炎症反应可能在颅内动脉粥样硬化和动脉扩张中起作用。