دورية أكاديمية
أعرض في EDS

Graft protective effects and donor-specific antibody suppression by CD4 + CD25 + Foxp3 + regulatory T cell induced by HMG-CoA reductase inhibitor rosuvastatin in a murine heart transplant model.

التفاصيل البيبلوغرافية
العنوان: Graft protective effects and donor-specific antibody suppression by CD4 + CD25 + Foxp3 + regulatory T cell induced by HMG-CoA reductase inhibitor rosuvastatin in a murine heart transplant model.
المؤلفون: Iguchi K; Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan., Yamamoto Y; Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan., Uchiyama M; Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan. mautiya@yahoo.co.jp., Masaoka H; Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan., Nakamura M; Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan., Shizuka H; Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan., Imazuru T; Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan., Shimokawa T; Department of Cardiovascular Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
المصدر: Journal of cardiothoracic surgery [J Cardiothorac Surg] 2024 Jun 25; Vol. 19 (1), pp. 368. Date of Electronic Publication: 2024 Jun 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101265113 Publication Model: Electronic Cited Medium: Internet ISSN: 1749-8090 (Electronic) Linking ISSN: 17498090 NLM ISO Abbreviation: J Cardiothorac Surg Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, 2006-
مواضيع طبية MeSH: Rosuvastatin Calcium*/pharmacology , Heart Transplantation* , T-Lymphocytes, Regulatory*/drug effects , T-Lymphocytes, Regulatory*/immunology , Hydroxymethylglutaryl-CoA Reductase Inhibitors*/pharmacology , Mice, Inbred C57BL* , Mice, Inbred CBA*, Animals ; Mice ; Graft Rejection/prevention & control ; Graft Rejection/immunology ; Graft Survival/drug effects ; Graft Survival/immunology ; Interleukin-2 Receptor alpha Subunit/immunology ; Male ; Forkhead Transcription Factors/metabolism ; Disease Models, Animal ; Flow Cytometry
مستخلص: Background: We previously demonstrated that the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (statins) play an important role in the regulation of alloimmune responses. However, little is known regarding the effects of statin on allograft protection or donor-specific antibodies (DSA). In this study, we investigated the graft-protective and immunomodulatory effects of rosuvastatin in a model of fully major histocompatibility complex-mismatched murine cardiac allograft transplantation.
Methods: CBA mice underwent transplantation of C57BL/6 (B6) hearts and received 50 and 500 μg/kg/day of rosuvastatin from the day of transplantation until seven days after the completion of transplantation. To confirm the requirement for regulatory T cells (Tregs), we administered an anti-interleukin-2 receptor alpha antibody (PC-61) to rosuvastatin-treated CBA recipients. Additionally, histological and fluorescent staining, cell proliferation analysis, flow cytometry, and DSA measurements were performed.
Results: CBA recipients with no treatment rejected B6 cardiac graft acutely (median survival time [MST], 7 days). CBA mice treated with 500 μg/kg/day of rosuvastatin prolonged allograft survival (MSTs, 77 days). Fluorescent staining studies showed that rosuvastatin-treated recipients had strong aggregation of CD4 + Foxp3 + cells in the myocardium and around the coronary arteries of cardiac allografts two weeks after grafting. Flow cytometry studies performed two weeks after transplantation showed an increased number of splenic CD4 + CD25 + Foxp3 + T cells in rosuvastatin-treated recipients. The addition of rosuvastatin to mixed leukocyte cultures suppressed cell proliferation by increasing the number of CD4 + CD25 + Foxp3 + Tregs. Additionally, Tregs suppressed DSA production in rosuvastatin-treated recipients.
Conclusion: Rosuvastatin treatment may be a complementary graft-protective strategy for suppressing DSA production in the acute phase, driven by the promotion of splenic and graft-infiltrating CD4 + CD25 + Foxp3 + Tregs.
(© 2024. The Author(s).)
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فهرسة مساهمة: Keywords: Cardiac transplant model; HMG-CoA reductase inhibitor; Mouse; Regulatory T cell; Rosuvastatin
المشرفين على المادة: 83MVU38M7Q (Rosuvastatin Calcium)
0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
0 (Interleukin-2 Receptor alpha Subunit)
0 (Forkhead Transcription Factors)
0 (Foxp3 protein, mouse)
تواريخ الأحداث: Date Created: 20240625 Date Completed: 20240626 Latest Revision: 20240715
رمز التحديث: 20240715
مُعرف محوري في PubMed: PMC11197312
DOI: 10.1186/s13019-024-02888-4
PMID: 38918849
قاعدة البيانات: MEDLINE
الوصف
تدمد:1749-8090
DOI:10.1186/s13019-024-02888-4