Distinct monocyte phenotypes are associated with peri-coronary inflammation in persons with and without HIV and without cardiovascular disease
12 affiliations
- 1Division of Infectious Diseases, Vanderbilt University Medical Center
- 2Department of Biostatistics, School of Community Health and Policy, Morgan State University
- 3Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine
- 4Rustbelt Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine
- 5Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University School of Medicine
- 6Section of Cardiothoracic Imaging, Department of Radiology, University of Maryland School of Medicine
- 7Section of Infectious Diseases, Department of Medicine, Boston Chobanian and Avedisian School of Medicine
- 8Department of Medicine, Washington University School of Medicine
- 9Department of Medicine, Institute of Human Virology, University of Maryland School of Medicine
- 10Division of Cardiology, Department of Medicine, Washington University School of Medicine
- 11Veteran’s Health Administration, Tennessee Valley Healthcare System
- 12Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University
Abstract
Background and objective: Chronic inflammation in persons with (PWH) and without HIV (PWoH) is linked to cardiovascular disease (CVD). The fat attenuation index (FAI), a marker of peri-coronary inflammation, predicts CVD risk. The relationship between FAI and monocyte phenotypes remains unclear. This study aimed to evaluate the relationship between monocyte subsets—classical (CD16dim intermediate/inflammatory monocytes and CD16neg), intermediate, and non-classical— and surface markers of activation and chemokine expression, and FAI in a cohort of PWH and PWoH, and compare relative differences by HIV serostatus.
Methods: In this cross-sectional of a prospective observational cohort study, 58 virologically suppressed PWH and 16 PWoH without known CVD underwent coronary computed tomography angiography to measure FAI. Peripheral blood monocyte subsets and activation/homing phenotypes were analyzed via flow cytometry. Multivariable regression models assessed correlations between monocyte markers and FAI in the LAD and RCA, with interaction terms testing effects of HIV serostatus.
Results: Frequency and expression of CD40 were elevated in PWH, while HLA-DR expression was lower across all monocyte subsets compared to PWoH. CD38 ⁺ intermediate monocytes were linked to worsened LAD FAI. CD38 ⁺ non-classical monocytes were correlated with worsened RCA FAI. CCR2 expression on total classical, and CD16dim, and CD16neg monocytes correlated with worsened RCA and LAD FAI, while CX3CR1 ⁺ monocytes and CD40 ⁺ subsets correlated with improved RCA FAI in adjusted analyses.
Conclusions: FAI demonstrates strong correlations with monocyte phenotypes with relationships influenced by HIV serostatus, highlighting activation markers and chemokine receptor profiles as plausible drivers of vascular inflammation and FAI as a tool for detecting early immune-mediated vascular inflammation.
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BibTeX
@article{stephens2026distinct,
title = {{Distinct monocyte phenotypes are associated with peri-coronary inflammation in persons with and without HIV and without cardiovascular disease}},
author = {Victoria R. Stephens and Mian B. Hossain and Joshua Nordman and Michael L. Freeman and Jean Jeudy and Shana AB Burrowes and Marcela Araujo de Oliveira Santana and Sarah E. Mitchell and Sumanth D. Prabhu and Michael M. Lederman and Celestine N. Wanjalla and Nicholas Funderburg and Shashwatee Bagchi},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1960785},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960785/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Distinct monocyte phenotypes are associated with peri-coronary inflammation in persons with and without HIV and without cardiovascular disease
AU - Victoria R. Stephens
AU - Mian B. Hossain
AU - Joshua Nordman
AU - Michael L. Freeman
AU - Jean Jeudy
AU - Shana AB Burrowes
AU - Marcela Araujo de Oliveira Santana
AU - Sarah E. Mitchell
AU - Sumanth D. Prabhu
AU - Michael M. Lederman
AU - Celestine N. Wanjalla
AU - Nicholas Funderburg
AU - Shashwatee Bagchi
PY - 2026
DA - 2026/10/20
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1960785
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960785/full
AB - Background and objective: Chronic inflammation in persons with (PWH) and without HIV (PWoH) is linked to cardiovascular disease (CVD). The fat attenuation index (FAI), a marker of peri-coronary inflammation, predicts CVD risk. The relationship between FAI and monocyte phenotypes remains unclear. This study aimed to evaluate the relationship between monocyte subsets—classical (CD16dim intermediate/inflammatory monocytes and CD16neg), intermediate, and non-classical— and surface markers of activation and chemokine expression, and FAI in a cohort of PWH and PWoH, and compare relative differences by HIV serostatus. Methods: In this cross-sectional of a prospective observational cohort study, 58 virologically suppressed PWH and 16 PWoH without known CVD underwent coronary computed tomography angiography to measure FAI. Peripheral blood monocyte subsets and activation/homing phenotypes were analyzed via flow cytometry. Multivariable regression models assessed correlations between monocyte markers and FAI in the LAD and RCA, with interaction terms testing effects of HIV serostatus. Results: Frequency and expression of CD40 were elevated in PWH, while HLA-DR expression was lower across all monocyte subsets compared to PWoH. CD38 ⁺ intermediate monocytes were linked to worsened LAD FAI. CD38 ⁺ non-classical monocytes were correlated with worsened RCA FAI. CCR2 expression on total classical, and CD16dim, and CD16neg monocytes correlated with worsened RCA and LAD FAI, while CX3CR1 ⁺ monocytes and CD40 ⁺ subsets correlated with improved RCA FAI in adjusted analyses. Conclusions: FAI demonstrates strong correlations with monocyte phenotypes with relationships influenced by HIV serostatus, highlighting activation markers and chemokine receptor profiles as plausible drivers of vascular inflammation and FAI as a tool for detecting early immune-mediated vascular inflammation.
SN - 1664-3224
ER -