title: Association of T Cell and Macrophage Activation with Arterial Vascular Health in HIV.
abstract: HIV-infected individuals are at increased risk of cardiovascular disease (CVD), but the arterial vascular functions affected by persistent innate and cellular immune activation are not well described. We assessed the relationship between immunologic and vascular parameters in 70 HIV-infected adults on efavirenz, tenofovir, and emtricitabine with more than 2 years of virologic suppression and no history of CVD. We measured brachial artery flow-mediated dilation (FMD) using ultrasound and circulating intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) by multiple immunoassay. We also measured circulating naive (CD45RO-CCR7+CD27+), activated (CD38+and CD38+DR+), exhausted (PD1+), senescent (CD57+), and memory (CD45RO+) CD4+and CD8+T cell subsets by flow cytometry, and macrophage activation markers by ELISA and multiple immunoassay. Regression models were adjusted for age, sex, smoking, duration of antiretroviral therapy (ART), and body mass index. Median age was 45 years (IQR 39, 50), median CD4+count 701 cells/μl (IQR 540, 954), and 43% were female. Lower brachial FMD was associated with a higher percentage of activated CD8+T cells (p < .01), but not associated with macrophage activation. In contrast, higher ICAM-1 and VCAM-1 were associated with sCD163 (p < = .01 for both), macrophage inflammatory protein-1α (p < = .02 for both), and sCD14 (p = .01 for ICAM-1 only). These findings are consistent with the hypothesis that circulating CD8+T cell activation may impair arterial smooth muscle relaxation, while macrophage activation has a role in the expression of endothelial cell proteins involved in immune cell translocation. Both innate and cellular immune activation appear to promote arterial vascular disease in HIV-infected persons on ART using differing mechanisms.
authors.affiliation: 1 Department of Medicine, Vanderbilt University Medical Center , Nashville, Tennessee.
authors.forename: Heather N
authors.initials: HN
authors.lastname: Grome
authors.affiliation: 2 Division of Infectious Diseases, Vanderbilt University Medical Center , Nashville, Tennessee.
authors.forename: Louise
authors.initials: L
authors.lastname: Barnett
authors.affiliation: 2 Division of Infectious Diseases, Vanderbilt University Medical Center , Nashville, Tennessee.
authors.forename: Cindy C
authors.initials: CC
authors.lastname: Hagar
authors.affiliation: 3 Division of Clinical Pharmacology, Vanderbilt University Medical Center , Nashville, Tennessee.|4 Center for Vascular Biology, Vanderbilt University Medical Center , Nashville, Tennessee.
authors.forename: David G
authors.initials: DG
authors.lastname: Harrison
authors.affiliation: 2 Division of Infectious Diseases, Vanderbilt University Medical Center , Nashville, Tennessee.|5 Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center , Nashville, Tennessee.
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.affiliation: 2 Division of Infectious Diseases, Vanderbilt University Medical Center , Nashville, Tennessee.
authors.forename: John R
authors.initials: JR
authors.lastname: Koethe
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use; D048588:Benzoxazines / Q000627:therapeutic use; D001916:Brachial Artery / Q000000981:diagnostic imaging; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D003521:Cyclopropanes; D000068679:Emtricitabine / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007118:Immunoassay; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D000068698:Tenofovir / Q000627:therapeutic use; D014463:Ultrasonography; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000068698:Tenofovir; D000068679:Emtricitabine; C098320:efavirenz
keywords: HIV; cardiovascular; endothelium; flow-mediated dilation; immune activation