Ly6C + Inflammatory Monocyte Differentiation Partially Mediates Hyperhomocysteinemia-Induced Vascular Dysfunction in Type 2 Diabetic db/db Mice
| العنوان: | Ly6C + Inflammatory Monocyte Differentiation Partially Mediates Hyperhomocysteinemia-Induced Vascular Dysfunction in Type 2 Diabetic db/db Mice |
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| المؤلفون: | Xinyuan Li, Jason Saredy, Hong Wang, Ramon Cueto, Pu Fang, Xiaohua Jiang, Xiaofeng Yang, Jixiang Xia, Huimin Shan |
| المصدر: | Arteriosclerosis, Thrombosis, and Vascular Biology. 39:2097-2119 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | medicine.medical_specialty, Hyperhomocysteinemia, Type 1 diabetes, business.industry, nutritional and metabolic diseases, Inflammation, Inflammatory monocyte, medicine.disease, Endocrinology, Diabetes mellitus, Internal medicine, cardiovascular system, Medicine, Risk factor, medicine.symptom, Cardiology and Cardiovascular Medicine, business |
| الوصف: | Objective: Hyperhomocysteinemia (HHcy) is a potent risk factor for diabetic cardiovascular diseases. We have previously reported that hyperhomocysteinemia potentiates type 1 diabetes mellitus-induced inflammatory monocyte differentiation, vascular dysfunction, and atherosclerosis. However, the effects of hyperhomocysteinemia on vascular inflammation in type 2 diabetes mellitus (T2DM) and the underlying mechanism are unknown. Approach and Results: Here, we demonstrate that hyperhomocysteinemia was induced by a high methionine diet in control mice (homocysteine 129 µmol/L), which was further worsened in T2DM db/db mice (homocysteine 180 µmol/L) with aggravated insulin intolerance. Hyperhomocysteinemia potentiated T2DM-induced mononuclear cell, monocyte, inflammatory monocyte (CD11b + Ly6C + ), and M1 macrophage differentiation in periphery and aorta, which were rescued by folic acid-based homocysteine-lowering therapy. Moreover, hyperhomocysteinemia exacerbated T2DM-impaired endothelial-dependent aortic relaxation to acetylcholine. Finally, transfusion of bone marrow cells depleted for Ly6C by Ly6c shRNA transduction improved insulin intolerance and endothelial-dependent aortic relaxation in hyperhomocysteinemia+T2DM mice. Conclusions: Hyperhomocysteinemia potentiated systemic and vessel wall inflammation and vascular dysfunction partially via inflammatory monocyte subset induction in T2DM. Inflammatory monocyte may be a novel therapeutic target for insulin resistance, inflammation, and cardiovascular complications in hyperhomocysteinemia+T2DM. |
| تدمد: | 1524-4636 1079-5642 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::76222c9ba5b7c2ecf2ec5523bf8bd10dTest https://doi.org/10.1161/atvbaha.119.313138Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........76222c9ba5b7c2ecf2ec5523bf8bd10d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244636 10795642 |
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