MicroRNA 29b-dependent mechanisms of arterial stiffness in diabetes.

糖尿病动脉硬化的 MicroRNA 29b 依赖性机制。

• 批准号: 430929322
• 负责人: Dr. Isabel Nahal Schellinger
• 金额: --
• 依托单位: Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/430929322?language=en
• 关键词: MicroRNA; 29b; dependent; mechanisms; arterial

Patients with type 2 diabetes (T2D) suffer from an increased risk of developing cardiovascular diseases (CVD), e.g., hypertension, heart failure, myocardial infarction, and stroke. A critical link between T2D and the accompanying increased risk for CVD might be arterial stiffening, a major complication of T2D. Till now, many biological processes (including extracellular matrix (ECM) remodeling, calcification, inflammation, and oxidative stress) have been recognized to contribute to diabetes-related arterial stiffness. Still, specific strategies for intervention remain elusive.Lately, non-coding RNAs have been identified as key regulators of cellular function in health and disease. One subclass of these non-coding RNAs are microRNAs (miRs) that may modulate complex biological processes – such as arterial stiffening – by inhibiting multiple target genes and therefore serve as promising target for therapeutical intervention. Another subclass of interest are circular RNAs (circRNAs) that serve as miR sponges and valuable biomarkers due to their resistance to peripheral degradation.Preliminary data show that miR-29b is downregulated in human as well as murine aortic tissue, and potentially interferes with genes orchestrating vascular matrix remodeling. Furthermore, we hypothesize that circHIPK3 might act as miR-29b sponge in the context of T2D. Thus, the proposed project investigates mechanisms regulating miR-29b under diabetic conditions, in addition to the role of miR-29b itself as a potential regulator of diabetes-related arterial stiffness.

2型糖尿病(T2D)患者患心血管疾病(CVD)的风险增加，例如高血压、心力衰竭、心肌梗死和中风。T2D与随之而来的心血管疾病风险增加之间的一个关键联系可能是动脉硬化，这是T2D的一个主要并发症。到目前为止，许多生物过程(包括细胞外基质(ECM)重构、钙化、炎症和氧化应激)被认为是糖尿病相关动脉僵硬的原因。尽管如此，干预的具体策略仍然缺乏。最近，非编码RNA已被确定为健康和疾病中细胞功能的关键调节因素。这些非编码RNA的一个亚类是microRNAs(MiRs)，它可以通过抑制多个靶基因来调节复杂的生物学过程，如动脉硬化，因此成为治疗干预的有希望的靶点。另一个令人感兴趣的亚类是环状RNA(CircRNAs)，它们作为miR海绵和有价值的生物标记物，因为它们对外周降解具有抵抗力。初步数据显示，miR-29b在人和小鼠的主动脉组织中下调，并可能干扰协调血管基质重构的基因。此外，我们假设CircHIPK3在T2D背景下可能作为miR-29b海绵。因此，除了miR-29b本身作为糖尿病相关动脉僵硬的潜在调节器之外，拟议的项目还研究在糖尿病条件下调节miR-29b的机制。