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Arterioscler Thromb Vasc Biol. 2014 May;34(5):1085-92. doi: 10.1161/ATVBAHA.113.303153. Epub 2014 Mar 20.

Macrophage inflammatory markers are associated with subclinical carotid artery disease in women with human immunodeficiency virus or hepatitis C virus infection.

Author information

1
From the Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA (I.S., K.L.); Department of Epidemiology & Population Health, Department of Medicine (D.B.H., D.T., K.A., R.K.), and Department of Obstetrics & Gynecology and Women's Health (K.A.), and Department of Microbiology & Immunology (V.P.), Albert Einstein College of Medicine, Bronx, NY; Department of Immunology/Microbiology, Rush University, Chicago, IL (J.P., M.C., A.L.L.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (E.T.G.); Division of Infectious Disease, Georgetown University Medical Center, Washington, DC (M.A.Y.); Department of Cardiovascular Disease, SUNY Downstate Medical Center, Brooklyn, NY (J.L.); Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA (R.K.); Department of Medicine, University of California, San Francisco (P.C.T.); Department of Cardiology, Angiology and Pneumonology, University of Heidelberg, Germany (C.G.); and Department of Medicine, University of California, San Diego (B.M.).

Abstract

OBJECTIVE:

Infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) may be associated with atherosclerosis and vascular disease. Macrophages are a major component of atherosclerotic plaque, and classically activated (M1) macrophages contribute to plaque instability. Our goal was to identify plasma biomarkers that reflect macrophage inflammation and are associated with subclinical atherosclerosis.

APPROACH AND RESULTS:

We tested whether M1 macrophages produce galectin-3-binding protein in vitro. Then, we measured galectin-3-binding protein and the soluble macrophage biomarkers soluble cluster of differentiation (CD) 163 and soluble CD14 in 264 participants in the Women's Interagency HIV Study. Women were positive for HIV, HCV, both, or neither (66 in each group, matched for age, race/ethnicity, and smoking status). Carotid artery disease was assessed by ultrasound measurement of right distal common carotid artery intima-media thickness, distensibility, and presence of atherosclerotic lesions (intima-media thickness >1.5 mm). Plasma galectin-3-binding protein was higher in HCV+ than HCV- women (P<0.01) but did not differ by HIV status. The 3 inflammatory macrophage markers were significantly correlated with each other and negatively correlated with CD4+ counts in HIV-infected women. We defined a macrophage score as 1, 2, or 3 biomarkers elevated above the median. In models adjusted for traditional risk factors, higher macrophage scores were significantly associated with increased atherosclerotic lesions and lower carotid distensibility. Receiver-operator curve analysis of lesions revealed that the markers added predictive value beyond traditional risk factors and C-reactive protein.

CONCLUSIONS:

The macrophage inflammatory markers galectin-3-binding protein, soluble CD163, and soluble CD14 are significantly associated with carotid artery disease in the setting of HIV and HCV infection.

KEYWORDS:

acquired immunodeficiency syndrome; atherosclerosis; immune system; risk factors; women

PMID:
24651679
PMCID:
PMC4067091
DOI:
10.1161/ATVBAHA.113.303153
[Indexed for MEDLINE]
Free PMC Article

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