Objective
Infection with hepatitis C (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
(Gal-3BP) in-vitro. Then we measured Gal-3BP and the soluble macrophage
biomarkers sCD163 and sCD14 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 (cIMT), distensibility,
and presence of atherosclerotic lesions (IMT>1.5 mm). Plasma Gal-3BP was
higher in HCV+ than HCV− women (p<0.01), but did not
differ by HIV status. The three 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 Gal-3BP, sCD163 and sCD14 are
significantly associated with carotid artery disease in the setting of HIV
and HCV infection.