title: 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.
abstract: 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 mm, FRS of 6%, a median viral load of 48 copies/mL, and CD4+ T cell count of 479 cells/μL. Soluble VCAM-1, and expansion of CD14dimCD16- 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.
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, HI, USA; Department of Tropical Medicine, John A. Burns School of Medicine, Honolulu, HI, USA. Electronic address: jbarbour@hawaii.edu.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Barbour
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, HI, USA; Department of Tropical Medicine, John A. Burns School of Medicine, Honolulu, HI, USA.
authors.forename: Emilie C
authors.initials: EC
authors.lastname: Jalbert
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, HI, USA; Department of Medicine, John A. Burns School of Medicine, Honolulu, HI, USA.
authors.forename: Dominic C
authors.initials: DC
authors.lastname: Chow
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, HI, USA; Department of Medicine, John A. Burns School of Medicine, Honolulu, HI, USA.
authors.forename: Louie Mar A
authors.initials: LM
authors.lastname: Gangcuangco
authors.affiliation: Blood Systems Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
authors.affiliation: Blood Systems Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Keating
authors.affiliation: Blood Systems Research Institute, San Francisco, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Heitman
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, HI, USA.
authors.forename: Lorna
authors.initials: L
authors.lastname: Nagamine
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, HI, USA; Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Seto
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, HI, USA; Department of Tropical Medicine, John A. Burns School of Medicine, Honolulu, HI, USA.
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, HI, USA; Department of Medicine, John A. Burns School of Medicine, Honolulu, HI, USA; Straub Clinics and Hospital, Honolulu, HI, USA.
authors.forename: Beau K
authors.initials: BK
authors.lastname: Nakamoto
authors.affiliation: Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA, USA.
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, HI, USA; Queen's Medical Center, Honolulu, HI, USA.
authors.forename: Nisha I
authors.initials: NI
authors.lastname: Parikh
authors.affiliation: Hawaii Center for AIDS, University of Hawaii, Honolulu, HI, USA; Department of Medicine, John A. Burns School of Medicine, Honolulu, HI, USA.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Shikuma
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000378:metabolism*; D002339:Carotid Arteries / Q000473:pathology*; D059168:Carotid Intima-Media Thickness; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D017452:Receptors, IgG / Q000378:metabolism; D012307:Risk Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D019010:Vascular Cell Adhesion Molecule-1
keywords: Biomarker; CD14; CIMT; Cardiovascular disease; Carotid intima-media; Cytokines; Framingham risk score; HIV; Monocytes; Regression; Screen; VCAM-1