Relationship between microbial translocation and endothelial function in HIV infected patients.
Relationship between microbial translocation and endothelial function in HIV infected patients.
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DOI：
10.1371/journal.pone.0042624
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dubé MP
中科院分区：
文献类型：
--
作者：
Blodget E;Shen C;Aldrovandi G;Rollie A;Gupta SK;Stein JH;Dubé MP
HIV 感染时微生物产物的循环水平会增加，并在其他疾病中引起内皮功能障碍。我们检查了印第安纳大学一项横断面单中心研究（印第安纳州，N = 85）和一项抗逆转录病毒治疗（ART）启动的 24 周多中心前瞻性研究（ACTG 5152s，N = 75）的数据。通过超声测量肱动脉血流介导的扩张（FMD）。从储存的样本中测量血浆脂多糖 (LPS) 和可溶性 CD14 (sCD14) 水平，并使用 Pearson 相关系数与 FMD 值进行关联。印第安纳州受试者中 63% 为男性，平均年龄 39 岁，中位 CD4 计数为 406 个细胞/mm3（388 个未接受 ART，464 个接受 ART）。 5152 名受试者中有 92% 为男性，平均年龄为 35 岁，入组时 CD4 计数中位数为 251 个细胞/mm3，在 ART 后增加至 396 个细胞/mm3。当单独或组合分析这两个队列时，sCD14 和 LPS 均未与 FMD 显着相关。在对接受 ART 的印第安纳州受试者（N = 46，平均 ART 持续时间 40 个月）的预先指定亚组分析中，LPS 与 FMD 呈负相关（r = −0.33，p = 0.02），但与 sCD14 无关（r = −0.01，p = 0.9）。多变量分析证实 LPS 是该亚组中 FMD 的独立预测因子 (p = 0.02)。 在接受长期 ART 的 HIV 感染者中，较高的 LPS 水平与较差的内皮功能相关，但在未经治疗的受试者或开始 ART 后 24 周时则不然。持续的微生物易位可能会导致动脉功能障碍，并增加长期接受 ART 的个体患心血管疾病的风险。
Circulating levels of microbial products are increased in HIV infection, and provoke endothelial dysfunction in other disease settings. We examined data from a cross-sectional single site study at Indiana University (Indiana, N = 85) and a 24- week multicenter prospective study of antiretroviral therapy (ART) initiation (ACTG 5152s, N = 75). Brachial artery flow-mediated dilation (FMD) was measured by ultrasound. Plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels were measured from stored specimens and correlated with FMD values using Pearson correlations. The Indiana subjects were 63% male with a mean age of 39 years and a median CD4 count of 406 cells/mm3 (388 not on ART, 464 on ART). The 5152s subjects were 92% were male with a mean age of 35 years and a median CD4 count of 251 cells/mm3 at entry which increased to 396 cells/mm3 on ART. When analyzing the two cohorts individually or in combination neither sCD14 nor LPS correlated significantly with FMD. In a pre-specified subgroup analysis of the Indiana subjects receiving ART (N = 46, mean ART duration 40 months) LPS was inversely correlated with FMD (r = −0.33, p = 0.02), but not sCD14 (r = −0.01, p = 0.9). Multivariate analysis confirmed LPS as an independent predictor of FMD in this subgroup (p = 0.02). In HIV- infected individuals on prolonged ART, higher LPS levels are associated with worse endothelial function but not in untreated subjects or at 24 weeks after ART initiation. Persistent microbial translocation may contribute to arterial dysfunction and the increased cardiovascular disease risk observed in individuals on long-term ART.
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