Alternative Splicing: A Key Mediator of Diabetic Vasculopathy.
Alternative Splicing: A Key Mediator of Diabetic Vasculopathy.
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DOI：
10.3390/genes12091332
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发表时间：
2021-08-27
期刊：
影响因子：
3.5
通讯作者：
Margariti A
中科院分区：
文献类型：
--
作者：
Cornelius VA;Fulton JR;Margariti A
心血管疾病是糖尿病患者死亡的主要原因。动脉粥样硬化是糖尿病血管并发症的主要驱动因素，糖尿病血管并发症是由高血糖和氧化应激对血管系统的有害影响引发的。研究广泛表明，糖尿病会导致血管的主要组成部分内皮功能障碍，导致严重的血管并发症。然而，糖尿病诱导血管功能障碍的致病机制在很大程度上仍不清楚。蛋白质编码前体mRNA的选择性剪接是基因表达的重要调控机制，并且被认为与细胞生理学交织在一起。最近，选择性剪接的作用已经在血管健康中出现，异常错误剪接在疾病发展中具有关键作用，包括在动脉粥样硬化中。本文综述了选择性剪接和选择性剪接异构体在血管系统中的作用，特别关注疾病状态。此外，我们探讨了最近阐明的选择性剪接的QKI基因内血管细胞生理学和糖尿病血管病变的发病。潜在的治疗策略，以恢复异常剪接进行了讨论。
Cardiovascular disease is the leading cause of death amongst diabetic individuals. Atherosclerosis is the prominent driver of diabetic vascular complications, which is triggered by the detrimental effects of hyperglycemia and oxidative stress on the vasculature. Research has extensively shown diabetes to result in the malfunction of the endothelium, the main component of blood vessels, causing severe vascular complications. The pathogenic mechanism in which diabetes induces vascular dysfunction, however, remains largely unclear. Alternative splicing of protein coding pre-mRNAs is an essential regulatory mechanism of gene expression and is accepted to be intertwined with cellular physiology. Recently, a role for alternative splicing has arisen within vascular health, with aberrant mis-splicing having a critical role in disease development, including in atherosclerosis. This review focuses on the current knowledge of alternative splicing and the roles of alternatively spliced isoforms within the vasculature, with a particular focus on disease states. Furthermore, we explore the recent elucidation of the alternatively spliced QKI gene within vascular cell physiology and the onset of diabetic vasculopathy. Potential therapeutic strategies to restore aberrant splicing are also discussed.
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影响因子：
6
作者：
Beazley-Long, Nicholas;Hua, Jing;Donaldson, Lucy F.
通讯作者：
Donaldson, Lucy F.
DOI：
10.1002/stem.2594
发表时间：
2017-04
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Cochrane A;Kelaini S;Tsifaki M;Bojdo J;Vilà-González M;Drehmer D;Caines R;Magee C;Eleftheriadou M;Hu Y;Grieve D;Stitt AW;Zeng L;Xu Q;Margariti A
通讯作者：
Margariti A
影响因子：
4.6
作者：
de Bruin RG;van der Veer EP;Prins J;Lee DH;Dane MJ;Zhang H;Roeten MK;Bijkerk R;de Boer HC;Rabelink TJ;van Zonneveld AJ;van Gils JM
通讯作者：
van Gils JM
影响因子：
8.2
作者：
Brouwers, O.;Niessen, P. M.;Haenen, G.;Miyata, T.;Brownlee, M.;Stehouwer, C. D.;De Mey, J. G.;Schalkwijk, C. G.
通讯作者：
Schalkwijk, C. G.
影响因子：
5.6
作者：
Failla CM;Carbo M;Morea V
通讯作者：
Morea V