دورية أكاديمية
Lysophosphatidylcholine trigger myocardial injury in diabetic cardiomyopathy via the TLR4/ZNF480/AP-1/NF-kB pathway
| العنوان: | Lysophosphatidylcholine trigger myocardial injury in diabetic cardiomyopathy via the TLR4/ZNF480/AP-1/NF-kB pathway |
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| المؤلفون: | Nannan Liu, Yang Chen, Tian An, Siyu Tao, Bohan Lv, Jinfang Dou, Ruxue Deng, Xianjie Zhen, Yuelin Zhang, Caizhong Lu, Zhongsheng Chang, Guangjian Jiang |
| المصدر: | Heliyon, Vol 10, Iss 13, Pp e33601- (2024) |
| بيانات النشر: | Elsevier, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Science (General) LCC:Social sciences (General) |
| مصطلحات موضوعية: | Diabetic cardiomyopathy, Lysophospholipids, Lipid metabolism, Gut microbiota, TLR4, ZNF480, Science (General), Q1-390, Social sciences (General), H1-99 |
| الوصف: | Background: Diabetic cardiomyopathy (DC), a frequent complication of type 2 diabetes mellitus (T2DM), is mainly associated with severe adverse outcomes. Previous research has highlighted the role of Lysophosphatidylcholine (LPC) in inducing myocardial injury; however, the specific mechanisms through which LPC mediate such injury in DC remain elusive. The existing knowledge gap underscores the need for additional clarification. Consequently, this study aimed to explore the impact and underlying mechanisms of LPC on myocardial injury in DC. Methods: A total of 55 patients diagnosed with T2DM and 62 healthy controls were involved. A combination of 16s rRNA sequencing, metabolomic analysis, transcriptomic RNA-sequencing (RNA-seq), and whole exome sequencing (WES) was performed on fecal and peripheral blood samples collected from the participants. Following this, correlation analysis was carried out, and the results were further validated through the mouse model of T2DM. Results: Four LPC variants distinguishing T2DM patients from healthy controls were identified, all of which were upregulated in T2DM patients. Specifically, Lysopc (16:0, 2 N isoform) and LPC (16:0) exhibited a positive correlation with nuclear factor kappa B subunit 2 (NFKB2) and a negative correlation with Zinc finger protein 480 (ZNF480) Furthermore, the expression levels of Toll-like receptor 4 (TLR4), c-Jun, c-Fos, and NFKB2 were upregulated in the peripheral blood of T2DM patients and in the myocardial tissue of T2DM mice, whereas ZNF480 expression level was downregulated. Lastly, myocardial injury was identified in T2DM mice. Conclusions: The results indicated that LPC could induce myocardial injury in DC through the TLR4/ZNF480/AP-1/NF-kB pathway, providing a precise target for the clinical diagnosis and treatment of DC. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2405-8440 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2405844024096324; https://doaj.org/toc/2405-8440 |
| DOI: | 10.1016/j.heliyon.2024.e33601 |
| URL الوصول: | https://doaj.org/article/10b26c0024204bc682cbd728d6bc1047 |
| رقم الأكسشن: | edsdoj.10b26c0024204bc682cbd728d6bc1047 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 24058440 |
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| DOI: | 10.1016/j.heliyon.2024.e33601 |