Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 34, Issue 5, Pages 1085-1092Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.113.303153
Keywords
acquired immunodeficiency syndrome; atherosclerosis; immune system; risk factors; women
Categories
Funding
- Women's Interagency HIV Study (WIHS
- Principal Investigators): UAB-MS WIHS [U01-AI-103401]
- Atlanta WIHS [U01-AI-103408]
- Bronx WIHS [U01-AI-035004]
- Brooklyn WIHS [U01-AI-031834]
- Chicago WIHS [U01-AI-034993]
- Metropolitan Washington WIHS [U01-AI-034994]
- Miami WIHS [U01-AI-103397]
- UNC WIHS [U01-AI-103390]
- Connie Wofsy Women's HIV Study, Northern California [U01-AI-034989]
- WIHS Data Management and Analysis Center [U01-AI-042590]
- Southern California WIHS [U01-HD-032632]
- National Institute of Allergy and Infectious Diseases (NIAID)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- National Cancer Institute (NCI)
- National Institute on Drug Abuse (NIDA)
- National Institute on Mental Health (NIMH)
- National Institute of Dental and Craniofacial Research (NIDCR)
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- National Institute on Deafness and other Communication Disorders (NIDCD)
- NIH Office of Research on Women's Health
- UCSF CTSA [UL1-TR000004]
- Atlanta CTSA [UL1-TR000454]
- American Heart Association postdoctoral fellowship
- [R01-HL-083760]
- [R01-HL-095140]
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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.
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