Linagliptin, A Xanthine-Based Dipeptidyl Peptidase-4 Inhibitor, Ameliorates Experimental Autoimmune Myocarditis
| العنوان: | Linagliptin, A Xanthine-Based Dipeptidyl Peptidase-4 Inhibitor, Ameliorates Experimental Autoimmune Myocarditis |
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| المؤلفون: | Mitsuaki Isobe, Yasuhiro Maejima, Natsuko Tamura, Yusuke Ito, Shun Nakagama, Takeshi Kasama, Kenzo Hirao, Yuka Shiheido-Watanabe, Tetsuo Sasano |
| المصدر: | JACC: Basic to Translational Science |
| بيانات النشر: | Elsevier BV, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, heart failure, Inflammation, Dipeptidyl peptidase-4 inhibitor, EAM, experimental autoimmune myocarditis, 030204 cardiovascular system & hematology, Pharmacology, Cathepsin G, Linagliptin, medicine.disease_cause, Dipeptidyl peptidase, 03 medical and health sciences, chemistry.chemical_compound, dipeptidyl peptidase 4, 0302 clinical medicine, ICIM, immune checkpoint inhibitor–induced myocarditis, medicine, Dipeptidyl peptidase-4, LVDd, left ventricular end-diastolic dimension, RORγt, RAR-related orphan nuclear receptor gamma, TMT, tandem mass tag, OHdG, hydroxyguanosine, ELISA, enzyme-linked immunosorbent assay, Xanthine, autoimmune myocarditis, 030104 developmental biology, chemistry, inflammation, DPP, dipeptidyl peptidase, Preclinical Research, medicine.symptom, Cardiology and Cardiovascular Medicine, Oxidative stress, medicine.drug |
| الوصف: | Visual Abstract Highlights • Treatment with linagliptin, a DPP-4 inhibitor, alleviates not only EAM but also ICIM. • DPP-4 physically interacts with cathepsin G and enhances its activity. • Linagliptin promotes SerpinA3N activity, thereby suppressing cathepsin G activity. • Cathepsin G aggravates EAM through upregulating angiotensin II. • Linagliptin suppresses oxidative stress in EAM hearts. Summary This study sought to show the mechanism of how to ameliorate experimental autoimmune myocarditis (EAM) by administering dipeptidyl peptidase (DPP)-4 inhibitor linagliptin. The number of RAR-related orphan nuclear receptor gamma–positive Th17 cells infiltrated to the EAM myocardium was significantly attenuated by linagliptin treatment. Tandem mass spectrometry–based analysis demonstrated that DPP-4 binds to cathepsin G in EAM hearts, thereby protecting cathepsin G activity through inhibiting SerpinA3N activity. Linagliptin suppresses oxidative stress in EAM hearts as well. Thus, we found that DPP-4 plays a detrimental role in the progression of EAM by interacting with cathepsin G, which, in turn, suppresses SerpinA3N activity. |
| تدمد: | 2452-302X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::65814fe3ecde72c1c9d187124a8133f6Test https://doi.org/10.1016/j.jacbts.2021.04.006Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....65814fe3ecde72c1c9d187124a8133f6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2452302X |
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