Academic Journal
Anti-Inflammatory Actions of Soluble Ninjurin-1 Ameliorate Atherosclerosis
| العنوان: | Anti-Inflammatory Actions of Soluble Ninjurin-1 Ameliorate Atherosclerosis |
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| المؤلفون: | Jeon, Sejin, Kim, Tae Kyeong, Jeong, Se-Jin, Jung, In-Hyuk, Kim, Nayoung, Lee, Mi-Ni, Sonn, Seong-Keun, Seo, Seungwoon, Jin, Jing, Kweon, Hyae Yon, Kim, Sinai, Shim, Dahee, Park, Young Mi, Lee, Sang-Hak, Kim, Kyu-Won, Cybulsky, Myron I., Shim, Hyunbo, Roh, Tae-Young, Park, Woong-Yang, Lee, Hae-Ock, Choi, Jae-Hoon, Park, Sung Ho, Oh, Goo Taeg |
| المصدر: | Circulation ; volume 142, issue 18, page 1736-1751 ; ISSN 0009-7322 1524-4539 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health) |
| سنة النشر: | 2020 |
| الوصف: | Background: Macrophages produce many inflammation-associated molecules, released by matrix metalloproteinases, such as adhesion molecules, and cytokines, as well, which play a crucial role in atherosclerosis. In this context, we investigated the relationship between Ninjurin-1 (Ninj1 [nerve injury-induced protein]), a novel matrix metalloproteinase 9 substrate, expression, and atherosclerosis progression. Methods: Ninj1 expression and atherosclerosis progression were assessed in atherosclerotic aortic tissue and serum samples from patients with coronary artery disease and healthy controls, and atheroprone apolipoprotein e–deficient ( Apoe −/− ) and wild-type mice, as well. Apoe −/− mice lacking systemic Ninj1 expression ( Ninj1 −/− Apoe −/− ) were generated to assess the functional effects of Ninj1. Bone marrow transplantation was also used to generate low-density lipoprotein receptor–deficient ( Ldlr −/− ) mice that lack Ninj1 specifically in bone marrow–derived cells. Mice were fed a Western diet for 5 to 23 weeks, and atherosclerotic lesions were investigated. The anti-inflammatory role of Ninj1 was verified by treating macrophages and mice with the peptides Ninj1 1 –56 (ML56) and Ninj1 26 –37 (PN12), which mimic the soluble form of Ninj1 (sNinj1). Results: Our in vivo results conclusively showed a correlation between Ninj1 expression in aortic macrophages and the extent of human and mouse atherosclerotic lesions. Ninj1 -deficient macrophages promoted proinflammatory gene expression by activating mitogen-activated protein kinase and inhibiting the phosphoinositide 3-kinase/Akt signaling pathway. Whole-body and bone marrow–specific Ninj1 deficiencies significantly increased monocyte recruitment and macrophage accumulation in atherosclerotic lesions through elevated macrophage-mediated inflammation. Macrophage Ninj1 was directly cleaved by matrix metalloproteinase 9 to generate a soluble form that exhibited antiatherosclerotic effects, as assessed in vitro and in vivo. Treatment with the sNinj1-mimetic ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1161/circulationaha.120.046907 |
| DOI: | 10.1161/CIRCULATIONAHA.120.046907 |
| الاتاحة: | http://dx.doi.org/10.1161/circulationaha.120.046907 https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.120.046907 |
| رقم الانضمام: | edsbas.4DA6D82B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1161/circulationaha.120.046907 |
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