3
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Circulatory CD4-Positive T-Lymphocyte Imbalance Mediated by Homocysteine-Induced AIM2 and NLRP1 Inflammasome Upregulation and Activation Is Associated with Human Abdominal Aortic Aneurysm

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction: CD4-positive T lymphocytes (CD4 cells) play a significant role in human abdominal aortic aneurysm (AAA). However, we know little about the role of the different CD4 subtypes. Objective: We aimed to discover the circulatory CD4 phenotypic marker profile and the roles of the newly found T helper cell 9 (Th9) and follicular helper T cells (Tfh) and that of inflammasomes in CD4 cells from AAA patients. Methods: We extracted CD4 cells from 30 AAA patients and 21 age-matched controls. Phenotype-specific transcription factors (TFs) and inflammasomes were analyzed with qRT-PCR. Results: Th17-, Th1-, Th9-, and Tfh-specific TFs and inflammasome components NLRP1 (NLR family pyrin domain-containing 1), NLRP3, NLRC4, AIM2 (absent in melanoma 2), PYCARD (apoptosis speck-like protein containing a CARD), and CASP1 (caspase 1) were upregulated, and T regulatory cell- and Th2-specific TFs were downregulated in the patients’ peripheral blood CD4 cells. Homocysteine was involved in Tfh and Th17 imbalance by AIM2 and NLRP1 inflammasome upregulation. Blood total cholesterol level correlated positively with NLRP1 expression, and blood low-density lipoprotein level correlated negatively with FOXP3 expression. Conclusions: Inflammasome-induced CD4 cell imbalance was involved in AAA. We thought that AAA might be a consequence of synergism between systemic immune imbalance and local autoimmunity.

          Related collections

          Most cited references 33

          • Record: found
          • Abstract: found
          • Article: not found

          The Multicentre Aneurysm Screening Study (MASS) into the effect of abdominal aortic aneurysm screening on mortality in men: a randomised controlled trial.

          Opposing views have been published on the importance of ultrasound screening for abdominal aortic aneurysms. The Multicentre Aneurysm Screening Study was designed to assess whether or not such screening is beneficial. A population-based sample of men (n=67800) aged 65-74 years was enrolled, and each individual randomly allocated to either receive an invitation for an abdominal ultrasound scan (invited group, n=33839) or not (control group, n=33961). Men in whom abdominal aortic aneurysms (> or =3 cm in diameter) were detected were followed-up with repeat ultrasound scans for a mean of 4.1 years. Surgery was considered on specific criteria (diameter > or =5.5 cm, expansion > or =1 cm per year, symptoms). Mortality data were obtained from the Office of National Statistics, and an intention-to-treat analysis was based on cause of death. Quality of life was assessed with four standardised scales. The primary outcome measure was mortality related to abdominal aortic aneurysm. 27147 of 33839 (80%) men in the invited group accepted the invitation to screening, and 1333 aneurysms were detected. There were 65 aneurysm-related deaths (absolute risk 0.19%) in the invited group, and 113 (0.33%) in the control group (risk reduction 42%, 95% CI 22-58; p=0.0002), with a 53% reduction (95% CI 30-64) in those who attended screening. 30-day mortality was 6% (24 of 414) after elective surgery for an aneurysm, and 37% (30 of 81) after emergency surgery. Our results provide reliable evidence of benefit from screening for abdominal aortic aneurysms.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Inflammasome activation by mitochondrial oxidative stress in macrophages leads to the development of angiotensin II-induced aortic aneurysm.

            Abdominal aortic aneurysm (AAA) is considered a chronic inflammatory disease; however, the molecular basis underlying the sterile inflammatory response involved in the process of AAA remains unclear. We previously showed that the inflammasome, which regulates the caspase-1-dependent interleukin-1β production, mediates the sterile cardiovascular inflammatory responses. Therefore, we hypothesized that the inflammasome is a key mediator of initial inflammation in AAA formation.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              IL-10 inhibits metalloproteinase and stimulates TIMP-1 production in human mononuclear phagocytes.

              Human mononuclear phagocytes can modulate the turnover of extracellular matrix by producing metalloproteinases such as 92-kD gelatinase and interstitial collagenase as well as the tissue inhibitor of metalloproteinases (TIMP). We have previously reported that IL-4 and IFN gamma released by lymphocytes suppress metalloproteinase biosynthesis in macrophages without affecting TIMP production (Lacraz, S., L. Nicod, B. C. de Rochementeix, C. Baumberger, J. Dayer, and H. Welgus. 1992. J. Clin. Invest. 90:382-388.; Shapiro, S. D., E. J. Campbell, D. K. Kobayashi, and H. G. Welgus 1990. J. Clin. Invest. 86:1204-1210). Like IL-4, IL-10 is secreted by Th2 lymphocytes and is inhibitory to several macrophage functions. In the present study, IL-10 was tested and compared to IL-2, IL-4, IL-6, and IFN gamma for its capacity to modulate synthesis of 92-kD gelatinase, interstitial collagenase and TIMP in human macrophages and monocytes. We found that IL-10, just like IL-4, inhibited the production of 92-kD gelatinase and blocked LPS-, as well as killed Staphylococcus aureus-induced, interstitial collagenase production. The principal finding of this study, however, was that IL-10, in distinction to IL-4, produced a dose-dependent stimulation in the biosynthesis of TIMP-1. TIMP-2 production was not affected. IL-10 regulated the expression of 92-kD gelatinase and TIMP-1 at the pretranslational level. Furthermore, IL-10 regulation was cell type-specific, as it had no effect on the production of metalloproteinases or TIMP by human fibroblasts. In summary, IL-10 has a potent and unique effect upon tissue macrophages and blood monocytes by enhancing TIMP-1 production while decreasing metalloproteinase biosynthesis.
                Bookmark

                Author and article information

                Journal
                JVR
                J Vasc Res
                10.1159/issn.1018-1172
                Journal of Vascular Research
                S. Karger AG
                1018-1172
                1423-0135
                2020
                September 2020
                01 July 2020
                : 57
                : 5
                : 276-290
                Affiliations
                aDepartment of Vascular Surgery, The First Hospital of China Medical University, Shenyang, China
                bLiaoning Provincial Key Laboratory of Aneurysm Etiology and Prevention, Shenyang, China
                Author notes
                *Shijie Xin, Department of Vascular Surgery, The First Hospital of China Medical University, NO.155, Nanjingbei Street, Shenyang 110001 (China), sjxin@cmu.edu.cn
                Article
                508077 J Vasc Res 2020;57:276–290
                10.1159/000508077
                32610319
                © 2020 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 9, Tables: 2, Pages: 15
                Categories
                Research Article

                Comments

                Comment on this article