ArticleThe Journal of clinical investigation2004
T cell-mediated vascular dysfunction of human allografts results from IFN-gamma dysregulation of NO synthase.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 102 citations in OpenAlex.
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- Decoding immune cell interactions during cardiac allograft vasculopathy: insights derived from bioinformatic strategies.Frontiers in cardiovascular medicine · 2025Review
- Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice.The Journal of clinical investigation · 2024Article
- Infiltration of Tumors Is Regulated by T cell-Intrinsic Nitric Oxide Synthesis.Cancer immunology research · 2023Article
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- New insights into maladaptive vascular responses to donor specific HLA antibodies in organ transplantation.Frontiers in transplantation · 2023Review
- Evaluation of salivary and serum methylated arginine metabolites and nitric oxide synthase in advanced periodontitis patients.Clinical oral investigations · 2022Article
- Targeting PCSK9 Ameliorates Graft Vascular Disease in Mice by Inhibiting NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells.Frontiers in immunology · 2022Article
- Regulation of T Cells in Cancer by Nitric Oxide.Cells · 2021Review
- The Immunopathology of Giant Cell Arteritis Across Disease Spectra.Frontiers in immunology · 2021Review
- Metabolites of the Nitric Oxide (NO) Pathway Are Altered and Indicative of Reduced NO and Arginine Bioavailability in Patients with Cardiometabolic Diseases Complicated with Chronic Wounds of Lower Extremities: Targeted Metabolomics Approach (LC-MS/MS).Oxidative medicine and cellular longevity · 2019Article
- The PD-1/PD-L1 Axis and Virus Infections: A Delicate Balance.Frontiers in cellular and infection microbiology · 2019Review
- Regulation of human T cell responses by dNP2-ctCTLA-4 inhibits human skin and microvessel graft rejection.Biomaterials · 2018Article
- Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2.Frontiers in physiology · 2018Article
- Rapamycin: A Bacteria-Derived Immunosuppressant That Has Anti-atherosclerotic Effects and Its Clinical Application.Frontiers in pharmacology · 2018Review
- Role of endoplasmic reticulum stress in the protective effects of PPARβ/δ activation on endothelial dysfunction induced by plasma from patients with lupus.Arthritis research & therapy · 2017Article
- Differential eNOS-signalling by platelet subpopulations regulates adhesion and aggregation.Cardiovascular research · 2017Review
- Transcriptional Activity of Gene Encoding Subunits R1 and R2 of Interferon Gamma Receptor in Peripheral Blood Mononuclear Cells in Patients with Slow Coronary Flow.Journal of medical biochemistry · 2016Article
- Vascular Dysfunction in Pneumocystis-Associated Pulmonary Hypertension Is Related to Endothelin Response and Adrenomedullin Concentration.The American journal of pathology · 2016Article
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8 authors at 1 institution in 1 country.
Funding
Abstract
Allograft vascular dysfunction predisposes to arteriosclerosis and graft loss. We examined how dysfunction develops in transplanted human arteries in response to circulating allogeneic T cells in vivo using immunodeficient murine hosts. Within 7-9 days, transplanted arteries developed endothelial cell (EC) dysfunction but remained sensitive to exogenous NO. By 2 weeks, the grafts developed impaired contractility and desensitization to NO, both signs of VSMC dysfunction. These T cell-dependent changes correlated with loss of eNOS and expression of iNOS--the latter predominantly within infiltrating T cells. Neutralizing IFN-gamma completely prevented both vascular dysfunction and changes in NOS expression; neutralizing TNF reduced IFN-gamma production and partially prevented dysfunction. Inhibiting iNOS partially preserved responses to NO at 2 weeks and reduced graft intimal expansion after 4 weeks in vivo. In vitro, memory CD4+ T cells acted on allogeneic cultured ECs to reduce eNOS activity and expression of protein and mRNA. These effects required T cell activation by class II MHC antigens and costimulators (principally lymphocyte function-associated antigen-3, or LFA-3) on the ECs and were mediated by production of soluble mediators including IFN-gamma and TNF. We conclude that IFN-gamma is a central mediator of vascular dysfunction and, through dysregulation of NOS expression, links early dysfunction with late arteriosclerosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.