Reduced CD14 expression on classical monocytes and vascular endothelial adhesion markers independently associate with carotid artery intima media thickness in chronically HIV-1 infected adults on virologically suppressive anti-retroviral therapy
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- 作者：Jason D. Barbour ; Emilie C. Jalbert ; Dominic C. Chow ; Louie Mar A. Gangcuangco ; Philip J. Norris ; Sheila M. Keating ; John Heitman ; Lorna Nagamine ; Todd Seto ; Lishomwa C. Ndhlovu ; Beau K. Nakamoto ; Howard N. Hodis ; Nisha I. Parikh ; Cecilia M. Shikuma
- 关键词：HIV ; Carotid intima-media ; CIMT ; Cardiovascular disease ; Framingham risk score ; Biomarker ; Screen ; Regression ; CD14 ; Monocytes ; VCAM-1 ; Cytokines
- 刊名：Atherosclerosis
- 出版年：January, 2014
- 年：2014
- 卷：232
- 期：1
- 页码：52-58
- 全文大小：547 K
文摘
HIV infection causes systemic immune inflammation, and increases the risk for cardiovascular (CVD) disease even among those on virologically suppressive anti-retroviral treatment (ART). We performed a biostatistical analysis and screen of candidate cellular and plasma biomarkers for association with carotid artery intima-media thickness (CIMT), independent of traditional CVD risk factors such as age, gender, systolic blood pressure (SBP), lipid levels, smoking and diabetes. We conducted a multi-stage analysis based on a cross-sectional study of CVD risk in HIV-infected subjects age >45 years on ART for >6 months. The goal of this analysis was to identify candidate cellular and plasma biomarkers of CIMT in HIV-1 infected adults. We further sought to determine if these candidate biomarkers were independent of traditional CVD risk factors previously identified in HIV negative adults. High-resolution B-mode ultrasound images of the right common carotid common artery (CCA) were obtained. Plasma soluble inflammatory mediators, cytokines and chemokines were detected. Monocytes were defined by CD14/CD16 expression, and CD8+ T-cell activation by CD38/HLA-DR expression. Subjects were a median of 49.5 years old, 87% male, had a CIMT of 0.73聽mm, FRS of 6%, a median viral load of 48 copies/mL, and CD4+ T cell count of 479 cells/渭L. Soluble VCAM-1, and expansion of CD14dimCD16鈭?monocytes each associated with higher CIMT independently of age and SBP. These factors are distinct components of a shared atherogenic process; 1) vascular endothelial molecular expression and 2) vascular monocytes that enter into the vascular endothelium and promote atherosclerotic plaque.