Celestine N Wanjalla1,2, Tecla M Temu3, Mona Mashayekhi4, Christian M Warren1, Bryan E Shepherd5, Rama Gangula1, Hubaida Fuseini1, Samuel Bailin1, Curtis L Gabriel6, Pandu Gangula7, Meena S Madhur8,9, Spyros Kalams1, Simon A Mallal1,2,10, David G Harrison8, Joshua A Beckman9, John R Koethe1,2,11. 1. Division of Infectious Diseases. 2. Tennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, Tennessee. 3. Departments of Global Health, University of Washington, Seattle, Washington. 4. Division of Diabetes, Endocrinology and Metabolism. 5. Department of Biostatistics. 6. Division of Gastroenterology, Vanderbilt University Medical Center, Nashville. 7. Department of Medicine & Dentistry, Meharry Medical College, Nashville. 8. Division of Clinical Pharmacology. 9. Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 10. Institute for Immunology and Infectious Diseases, Murdoch University, Western Australia, Australia. 11. Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
Abstract
OBJECTIVE: Chronic inflammation contributes to the high burden of cardiovascular disease (CVD) in persons with HIV (PWH). HIV has broad effects on innate and adaptive immune cells, including innate lymphoid cells (ILCs) and CD4+ T-helper cells. At present, the relationship between CVD and plasma cytokines reflecting ILC/T-helper responses in PWH is not well defined. We investigated relationships between plasma cytokines and subclinical atherosclerosis. DESIGN: A cross-sectional study. METHODS: We recruited 70 PWH on a single antiretroviral regimen (efavirenz, teno- fovir, and emtricitabine) with at least 12 months of suppressed viremia and 30 HIVnegative controls. We quantified plasma cytokines and chemokines, including inter- feron-g, interleukin (IL)-4, IL-13, and IL-17A, markers of macrophage activation, and markers of endothelial activation using multiplex assays and ELISA. Cytokines were grouped using Ward's hierarchical clustering. Brachial artery flow-mediated dilation (FMD) and carotid plaque burden were determined using ultrasound. Multivariable linear regression and negative binomial regression analyses were used to assess the relationships of plasma biomarkers and endpoints adjusted for CVD risk factors. RESULTS: We identified three distinct clusters in PWH, one containing Th1/Th2/ILC1/ ILC2 type cytokines, one with Th17/ILC3/macrophage-related cytokines, and a less specific third cluster. Lower FMD was associated with higher plasma IL-17A and macrophage inflammatory protein-1 a. In contrast, IL-4, a Th2/ILC2 type cytokine, was associated with carotid plaque. When HIV-negative controls were added to the models clustering was more diffuse, and these associations were attenuated or absent. CONCLUSION: Th17/ILC3 and Th2/ILC2-mediated immune mechanisms may have distinct roles in endothelial dysfunction and atherosclerotic plaque formation, respectively, in PWH.
OBJECTIVE: Chronic inflammation contributes to the high burden of cardiovascular disease (CVD) in persons with HIV (PWH). HIV has broad effects on innate and adaptive immune cells, including innate lymphoid cells (ILCs) and CD4+ T-helper cells. At present, the relationship between CVD and plasma cytokines reflecting ILC/T-helper responses in PWH is not well defined. We investigated relationships between plasma cytokines and subclinical atherosclerosis. DESIGN: A cross-sectional study. METHODS: We recruited 70 PWH on a single antiretroviral regimen (efavirenz, teno- fovir, and emtricitabine) with at least 12 months of suppressed viremia and 30 HIVnegative controls. We quantified plasma cytokines and chemokines, including inter- feron-g, interleukin (IL)-4, IL-13, and IL-17A, markers of macrophage activation, and markers of endothelial activation using multiplex assays and ELISA. Cytokines were grouped using Ward's hierarchical clustering. Brachial artery flow-mediated dilation (FMD) and carotid plaque burden were determined using ultrasound. Multivariable linear regression and negative binomial regression analyses were used to assess the relationships of plasma biomarkers and endpoints adjusted for CVD risk factors. RESULTS: We identified three distinct clusters in PWH, one containing Th1/Th2/ILC1/ ILC2 type cytokines, one with Th17/ILC3/macrophage-related cytokines, and a less specific third cluster. Lower FMD was associated with higher plasma IL-17A and macrophage inflammatory protein-1 a. In contrast, IL-4, a Th2/ILC2 type cytokine, was associated with carotid plaque. When HIV-negative controls were added to the models clustering was more diffuse, and these associations were attenuated or absent. CONCLUSION: Th17/ILC3 and Th2/ILC2-mediated immune mechanisms may have distinct roles in endothelial dysfunction and atherosclerotic plaque formation, respectively, in PWH.
Authors: Christian Erbel; Thomas J Dengler; Susanne Wangler; Felix Lasitschka; Florian Bea; Nadine Wambsganss; Maani Hakimi; Dittmar Böckler; Hugo A Katus; Christian A Gleissner Journal: Basic Res Cardiol Date: 2010-12-01 Impact factor: 17.165
Authors: Z Mallat; S Besnard; M Duriez; V Deleuze; F Emmanuel; M F Bureau; F Soubrier; B Esposito; H Duez; C Fievet; B Staels; N Duverger; D Scherman; A Tedgui Journal: Circ Res Date: 1999-10-15 Impact factor: 17.367
Authors: Meena S Madhur; Samuel A Funt; Li Li; Antony Vinh; Wei Chen; Heinrich E Lob; Yoichiro Iwakura; Yelena Blinder; Ayaz Rahman; Arshed A Quyyumi; David G Harrison Journal: Arterioscler Thromb Vasc Biol Date: 2011-04-07 Impact factor: 8.311
Authors: Daniel R Neill; See Heng Wong; Agustin Bellosi; Robin J Flynn; Maria Daly; Theresa K A Langford; Christine Bucks; Colleen M Kane; Padraic G Fallon; Richard Pannell; Helen E Jolin; Andrew N J McKenzie Journal: Nature Date: 2010-03-03 Impact factor: 49.962
Authors: Renata Mezomo Soccal; José Antonio Mainardi de Carvalho; Guilherme Vargas Bochi; Rafael Noal Moresco; José Edson Paz da Silva Journal: Biomed Pharmacother Date: 2016-03-14 Impact factor: 6.529
Authors: Meena S Madhur; Heinrich E Lob; Louise A McCann; Yoichiro Iwakura; Yelena Blinder; Tomasz J Guzik; David G Harrison Journal: Hypertension Date: 2009-12-28 Impact factor: 10.190