Zidar David A, Juchnowski Steven, Ferrari Brian, Clagett Brian, Pilch-Cooper Heather A, Rose Shawn, Rodriguez Benigno, McComsey Grace A, Sieg Scott F, Mehta Nehal N, Lederman Michael M, Funderburg Nicholas T
*Harrington Heart & Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH; †Department of Medicine, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH; ‡National Heart, Lung and Blood Institute, Section of Inflammation and Cardiometabolic Diseases, Bethesda, MD; §National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD; ‖Rainbow Babies and Children's Hospital, Cleveland, OH; and ¶Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, Ohio State University, Columbus, OH.
J Acquir Immune Defic Syndr. 2015 Jun 1;69(2):154-60. doi: 10.1097/QAI.0000000000000566.
HIV infection is associated with increased cardiovascular risk, and this risk correlates with markers of monocyte activation. We have shown that HIV is associated with a prothrombotic monocyte phenotype, which can be partially mitigated by statin therapy. We therefore explored the relationship between oxidized low-density lipoprotein (oxLDL) particles and monocyte activation.
We performed phenotypic analysis of monocytes using flow cytometry on fresh whole blood in 54 patients with HIV and 24 controls without HIV. Plasma levels of oxLDL, soluble CD14, IL-6, and soluble CD163 were measured by enzyme-linked immunosorbent assay. In vitro experiments were performed using flow cytometry.
Plasma levels of oxLDL were significantly increased in HIV infection compared with controls (60.1 units vs. 32.1 units, P < 0.001). Monocyte expression of the oxLDL receptors, CD36 and Toll-like receptor 4, was also increased in HIV. OxLDL levels correlated with markers of monocyte activation, including soluble CD14, tissue factor expression on inflammatory monocytes, and CD36. In vitro stimulation with oxLDL, but not to low-density lipoprotein, resulted in expansion of inflammatory monocytes and increased monocyte expression of tissue factor, recapitulating the monocyte profile we find in HIV disease.
OxLDL may contribute to monocyte activation, and further study in the context of HIV disease is warranted.
HIV感染与心血管风险增加相关，且这种风险与单核细胞活化标志物相关。我们已表明HIV与促血栓形成的单核细胞表型相关，他汀类药物治疗可部分减轻这种表型。因此，我们探讨了氧化型低密度脂蛋白（oxLDL）颗粒与单核细胞活化之间的关系。
我们对54例HIV患者的新鲜全血和24例未感染HIV的对照者进行了流式细胞术单核细胞表型分析。采用酶联免疫吸附测定法检测血浆中oxLDL、可溶性CD14、IL-6和可溶性CD163的水平。使用流式细胞术进行体外实验。
与对照组相比，HIV感染患者血浆中oxLDL水平显著升高（60.1单位对32.1单位，P < 0.001）。HIV患者单核细胞中oxLDL受体CD36和Toll样受体4的表达也增加。oxLDL水平与单核细胞活化标志物相关，包括可溶性CD14、炎性单核细胞上的组织因子表达和CD36。用oxLDL而非低密度脂蛋白进行体外刺激，导致炎性单核细胞扩增并增加单核细胞组织因子的表达，重现了我们在HIV疾病中发现的单核细胞特征。
oxLDL可能促成单核细胞活化，有必要在HIV疾病背景下进行进一步研究。
