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

Iftach Shaked, David B. Hanna, Christian Gleißner, Brenda Marsh, Jill Plants, Daniel Tracy, Kathryn Anastos, Mardge Cohen, Elizabeth T. Golub, Roksana Karim, Jason Lazar, Vinayaka R. Prasad, Phyllis C. Tien, Mary A. Young, Alan L. Landay, Robert C. Kaplan, Klaus Ley

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1085-1092
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume34
Issue number5
DOIs
StatePublished - 2014

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Carotid Artery Diseases
Virus Diseases
Hepacivirus
Macrophages
HIV
Galectin 3
Carrier Proteins
Biomarkers
Atherosclerosis
Carotid Intima-Media Thickness
Common Carotid Artery
Atherosclerotic Plaques
CD4 Lymphocyte Count
Vascular Diseases
C-Reactive Protein
Research Design
Age Groups
Smoking
Inflammation

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Macrophage inflammatory markers are associated with subclinical carotid artery disease in women with human immunodeficiency virus or hepatitis C virus infection. / Shaked, Iftach; Hanna, David B.; Gleißner, Christian; Marsh, Brenda; Plants, Jill; Tracy, Daniel; Anastos, Kathryn; Cohen, Mardge; Golub, Elizabeth T.; Karim, Roksana; Lazar, Jason; Prasad, Vinayaka R.; Tien, Phyllis C.; Young, Mary A.; Landay, Alan L.; Kaplan, Robert C.; Ley, Klaus.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 34, No. 5, 2014, p. 1085-1092.

Research output: Contribution to journalArticle

Shaked, Iftach ; Hanna, David B. ; Gleißner, Christian ; Marsh, Brenda ; Plants, Jill ; Tracy, Daniel ; Anastos, Kathryn ; Cohen, Mardge ; Golub, Elizabeth T. ; Karim, Roksana ; Lazar, Jason ; Prasad, Vinayaka R. ; Tien, Phyllis C. ; Young, Mary A. ; Landay, Alan L. ; Kaplan, Robert C. ; Ley, Klaus. / Macrophage inflammatory markers are associated with subclinical carotid artery disease in women with human immunodeficiency virus or hepatitis C virus infection. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2014 ; Vol. 34, No. 5. pp. 1085-1092.
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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.",
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AU - Shaked, Iftach

AU - Hanna, David B.

AU - Gleißner, Christian

AU - Marsh, Brenda

AU - Plants, Jill

AU - Tracy, Daniel

AU - Anastos, Kathryn

AU - Cohen, Mardge

AU - Golub, Elizabeth T.

AU - Karim, Roksana

AU - Lazar, Jason

AU - Prasad, Vinayaka R.

AU - Tien, Phyllis C.

AU - Young, Mary A.

AU - Landay, Alan L.

AU - Kaplan, Robert C.

AU - Ley, Klaus

PY - 2014

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N2 - 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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