دورية أكاديمية
miR‐29 contributes to normal endothelial function and can restore it in cardiometabolic disorders
العنوان: | miR‐29 contributes to normal endothelial function and can restore it in cardiometabolic disorders |
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المؤلفون: | Michael E Widlansky, David M Jensen, Jingli Wang, Yong Liu, Aron M Geurts, Alison J Kriegel, Pengyuan Liu, Rong Ying, Guangyuan Zhang, Marc Casati, Chen Chu, Mobin Malik, Amberly Branum, Michael J Tanner, Sudhi Tyagi, Kristie Usa, Mingyu Liang |
المصدر: | EMBO Molecular Medicine, Vol 10, Iss 3, Pp n/a-n/a (2018) |
بيانات النشر: | Springer Nature, 2018. |
سنة النشر: | 2018 |
المجموعة: | LCC:Medicine (General) LCC:Genetics |
مصطلحات موضوعية: | diabetes, endothelium, hypertension, microRNA, nitric oxide, Medicine (General), R5-920, Genetics, QH426-470 |
الوصف: | Abstract We investigated the role of microRNAs (miRNA) in endothelial dysfunction in the setting of cardiometabolic disorders represented by type 2 diabetes mellitus (T2DM). miR‐29 was dysregulated in resistance arterioles obtained by biopsy in T2DM patients. Intraluminal delivery of miR‐29a‐3p or miR‐29b‐3p mimics restored normal endothelium‐dependent vasodilation (EDVD) in T2DM arterioles that otherwise exhibited impaired EDVD. Intraluminal delivery of anti‐miR‐29b‐3p in arterioles from non‐DM human subjects or rats or targeted mutation of Mir29b‐1/a gene in rats led to impaired EDVD and exacerbation of hypertension in the rats. miR‐29b‐3p mimic increased, while anti‐miR‐29b‐3p or Mir29b‐1/a gene mutation decreased, nitric oxide levels in arterioles. The mutation of Mir29b‐1/a gene led to preferential differential expression of genes related to nitric oxide including Lypla1. Lypla1 was a direct target of miR‐29 and could abrogate the effect of miR‐29 in promoting nitric oxide production. Treatment with Lypla1 siRNA improved EDVD in arterioles obtained from T2DM patients or Mir29b‐1/a mutant rats or treated with anti‐miR‐29b‐3p. These findings indicate miR‐29 is required for normal endothelial function in humans and animal models and has therapeutic potential for cardiometabolic disorders. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1757-4684 1757-4676 |
Relation: | https://doaj.org/toc/1757-4676; https://doaj.org/toc/1757-4684 |
DOI: | 10.15252/emmm.201708046 |
URL الوصول: | https://doaj.org/article/952f272fb18645b9b1998da60a033318 |
رقم الأكسشن: | edsdoj.952f272fb18645b9b1998da60a033318 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 17574684 17574676 |
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DOI: | 10.15252/emmm.201708046 |