Non-Classical Monocytes and Monocyte Chemoattractant Protein-1 (MCP-1) Correlate with Coronary Artery Calcium Progression in Chronically HIV-1 Infected Adults on Stable Antiretroviral Therapy.
Non-Classical Monocytes and Monocyte Chemoattractant Protein-1 (MCP-1) Correlate with Coronary Artery Calcium Progression in Chronically HIV-1 Infected Adults on Stable Antiretroviral Therapy.
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DOI：
10.1371/journal.pone.0149143
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Chow DC
中科院分区：
文献类型：
--
作者：
Zungsontiporn N;Tello RR;Zhang G;Mitchell BI;Budoff M;Kallianpur KJ;Nakamoto BK;Keating SM;Norris PJ;Ndhlovu LC;Souza SA;Shikuma CM;Chow DC
持续的炎症和免疫激活被认为是慢性HIV感染患者亚临床动脉粥样硬化和心血管疾病（CVD）风险增加的原因。在这项研究中，我们通过心脏计算机断层扫描检测了外周血单核细胞亚群和可溶性炎症生物标志物与冠状动脉钙（CAC）进展的相关性。我们利用夏威夷老化与HIV-心血管研究中78名接受稳定抗逆转录病毒治疗（ART）的HIV感染参与者的基线数据进行了纵向分析，这些参与者在基线和2年随访时有可用的基线单核细胞亚群分析和CAC测量。通过流式细胞术评估低温保存血液中的单核细胞表型，并在高灵敏度Milliplex Luminex平台上使用抗体包被珠检测血浆中的可溶性生物标志物。2年内CAC的变化作为主要结局变量进行分析。在所有检测的单核细胞亚群和生物标志物中，较高的非经典单核细胞百分比（ρ = 0.259, p = 0.022）、白细胞介素(IL)-6 （ρ = 0.311, p = 0.012）和单核细胞化学引诱蛋白(MCP)-1 （ρ = 0.524, p = <0.001）与未调整的Spearman相关性中较高的2年CAC进展显著相关。非经典单核细胞百分比（ρ = 0.247, p = 0.039）和MCP-1 （ρ = 0.487, p = <0.001）与2年CAC进展仍有显著相关性，而IL-6在调整年龄、高血压、糖尿病、总/高密度脂蛋白胆固醇比、吸烟史和BMI后无显著相关性（ρ = 0.209, p = 0.120）。非经典单核细胞百分比和血浆MCP-1水平与CAC进展独立相关，并且可能与稳定抗逆转录病毒治疗下慢性HIV感染相关的动脉粥样硬化进展和CVD风险增加有关。
Persistent inflammation and immune activation has been hypothesized to contribute to increased prevalence of subclinical atherosclerosis and cardiovascular disease (CVD) risk in patients with chronic HIV infection. In this study, we examined the correlation of peripheral monocyte subsets and soluble biomarkers of inflammation to coronary artery calcium (CAC) progression, as measured by cardiac computed tomography scan. We conducted a longitudinal analysis utilizing baseline data of 78 participants with HIV infection on stable antiretroviral therapy (ART) in the Hawaii Aging with HIV-Cardiovascular study who had available baseline monocyte subset analysis as well as CAC measurement at baseline and at 2-year follow up. Monocyte phenotypes were assessed from cryopreserved blood by flow cytometry and plasma was assayed for soluble biomarkers using antibody-coated beads in a high sensitivity Milliplex Luminex platform. Change in CAC over 2 years was analyzed as the primary outcome variable. Of all monocyte subsets and biomarkers tested, higher non-classical monocyte percentage (ρ = 0.259, p = 0.022), interleukin (IL)-6 (ρ = 0.311, p = 0.012), and monocyte chemoattractant protein (MCP)-1 (ρ = 0.524, p = <0.001) were significantly correlated to higher 2-year CAC progression in unadjusted Spearman’s correlation. Non-classical monocyte percentage (ρ = 0.247, p = 0.039), and MCP-1 (ρ = 0.487, p = <0.001), remained significantly correlated to 2-year CAC progression, while IL-6 was not (ρ = 0.209, p = 0.120) after adjustment for age, hypertension, diabetes mellitus, total/HDL cholesterol ratio, smoking history, and BMI. The percentage of non-classical monocytes and plasma MCP-1 levels were independently associated with CAC progression and may be related to the progression of atherosclerosis and increased CVD risk associated with chronic HIV infection on stable ART.