دورية أكاديمية
Increased Macrophage-Specific Arterial Infiltration Relates to Noncalcified Plaque and Systemic Immune Activation in People With Human Immunodeficiency Virus.
| العنوان: | Increased Macrophage-Specific Arterial Infiltration Relates to Noncalcified Plaque and Systemic Immune Activation in People With Human Immunodeficiency Virus. |
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| المؤلفون: | Toribio M; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Wilks MQ; Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Hedgire S; Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Lu MT; Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Cetlin M; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Wang M; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Alhallak I; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Durbin CG; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., White KS; Biology Department, Boston College, Chestnut Hill, Massachusetts, USA., Wallis Z; Biology Department, Boston College, Chestnut Hill, Massachusetts, USA., Schnittman SR; Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Stanley TL; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., El-Fakhri G; Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Lee H; Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Autissier P; Biology Department, Boston College, Chestnut Hill, Massachusetts, USA., Zanni MV; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Williams KC; Biology Department, Boston College, Chestnut Hill, Massachusetts, USA., Grinspoon SK; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. |
| المصدر: | The Journal of infectious diseases [J Infect Dis] 2022 Nov 11; Vol. 226 (10), pp. 1823-1833. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0413675 Publication Model: Print Cited Medium: Internet ISSN: 1537-6613 (Electronic) Linking ISSN: 00221899 NLM ISO Abbreviation: J Infect Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Jan. 2011- : Oxford : Oxford University Press Original Publication: 1904-2010 : Chicago, IL : University of Chicago Press |
| مواضيع طبية MeSH: | Plaque, Atherosclerotic*/diagnostic imaging , HIV Infections*/drug therapy , Atherosclerosis*, Humans ; Macrophages ; HIV |
| مستخلص: | Background: Persistent immune activation is thought to contribute to heightened atherosclerotic cardiovascular disease (ASCVD) risk among people with human immunodeficiency virus (PWH). Methods: Participants (≥18 years) with or without human immunodeficiency virus (HIV) and without history of clinical ASCVD were enrolled. We hypothesized that increased macrophage-specific arterial infiltration would relate to plaque composition and systemic immune activation among PWH. We applied a novel targeted molecular imaging approach (technetium-99m [99mTc]-tilmanocept single photon emission computed tomography [SPECT]/CT) and comprehensive immune phenotyping. Results: Aortic 99mTc-tilmanocept uptake was significantly higher among PWH (n = 20) than participants without HIV (n = 10) with similar 10-year ASCVD risk (P = .02). Among PWH, but not among participants without HIV, noncalcified aortic plaque volume related directly to aortic 99mTc-tilmanocept uptake at different uptake thresholds. An interaction (P = .001) was seen between HIV status and noncalcified plaque volume, but not calcified plaque (P = .83). Systemic levels of caspase-1 (P = .004), CD14-CD16+ (nonclassical/patrolling/homing) monocytes (P = .0004) and CD8+ T cells (P = .005) related positively and CD4+/CD8+ T-cell ratio (P = .02) inversely to aortic 99mTc-tilmanocept uptake volume. Conclusions: Macrophage-specific arterial infiltration was higher among PWH and related to noncalcified aortic plaque volume only among PWH. Key systemic markers of immune activation relating to macrophage-specific arterial infiltration may contribute to heightened ASCVD risk among PWH. Clinical Trials Registration: NCT02542371. Competing Interests: Potential conflicts of interest. M. T. L. reports grant funding to his institution from AstraZeneca/MedImmune and Kowa Pharmaceuticals and consulting fees from PQBypass, unrelated to the present project. T. L. S. reports unrelated grant funding to her institution from Pfizer and Novo Nordisk. M. V. Z. is principal investigator of an industry-sponsored research grant from Gilead Sciences to her institution, unrelated to the present project. S. K. G. has grant funding to his institution from Gilead Sciences, KOWA Pharmaceuticals, and Theratechnologies, unrelated to the present project, and serves as a consultant for Theratechnologies, Regeneron, and ViiV Healthcare. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) |
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| معلومات مُعتمدة: | P30 DK040561 United States DK NIDDK NIH HHS; 8 UL 1TR000170 and 1 UL 1TR001102 United States TR NCATS NIH HHS; P30AI060354 United States NH NIH HHS; K24AI157882) United States NH NIH HHS; K24 AI157882 United States AI NIAID NIH HHS; K23 HL147799 United States HL NHLBI NIH HHS; P30DK040561 United States NH NIH HHS; P30 AI060354 United States AI NIAID NIH HHS; United States AHA American Heart Association-American Stroke Association; 1K23HL147799-01 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: CD206; HIV; NLRP3 inflammasome; SPECT; T-cell senescence; arterial inflammation; caspase-1; macrophages; noncalcified plaque; tilmanocept |
| سلسلة جزيئية: | ClinicalTrials.gov NCT02542371 |
| المشرفين على المادة: | 0 (technetium-diethylenetriaminepentaacetic acid-mannosyl-dextran) |
| تواريخ الأحداث: | Date Created: 20220720 Date Completed: 20221114 Latest Revision: 20230721 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC10205602 |
| DOI: | 10.1093/infdis/jiac301 |
| PMID: | 35856671 |
| قاعدة البيانات: | MEDLINE |
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