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2 型糖尿病中纤溶酶原激活物抑制剂-1 的昼夜节律与心血管并发症。

Circadian rhythm of plasminogen activator inhibitor-1 and cardiovascular complications in type 2 diabetes.

机构信息

Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao, China.

出版信息

Front Endocrinol (Lausanne). 2023 Mar 20;14:1124353. doi: 10.3389/fendo.2023.1124353. eCollection 2023.

Abstract

Cardiovascular complications are a common death cause in type 2 diabetes patients, as they are often combined. Plasminogen-activator Inhibitor 1 (PAI-1) participates in the development and progression of cardiovascular complications in diabetes. Insulin resistance increases PAI-1 production, and high PAI-1 levels lead to an environment conducive to thrombosis and earlier and more severe vascular disease. Current evidence also suggests that PAI-1 has a rhythmic profile of circadian fluctuations and acrophase in the morning within a single day, which might explain the high morning incidence of cardiovascular events. Thus, PAI-1 is a possible drug target. Although several PAI-1 inhibitors have been developed, none have yet been allowed for clinical use. Research on rhythm has also led to the concept of "chronotherapy", a rhythm-based drug regimen expected to improve the treatment of cardiovascular complications in diabetic patients. Herein, we searched several databases and reviewed relevant articles to describe the circadian rhythm characteristics and endogenous molecular mechanisms of PAI-1, its relationship with insulin resistance, the causes of cardiovascular complications caused by PAI-1, and the current development of PAI-1 inhibitors. We also summarized the possibility of using the circadian rhythm of PAI-1 to treat cardiovascular complications in diabetic patients.

摘要

心血管并发症是 2 型糖尿病患者常见的死亡原因,因为它们常常同时存在。纤溶酶原激活物抑制剂 1(PAI-1)参与糖尿病心血管并发症的发生和发展。胰岛素抵抗会增加 PAI-1 的产生,而高水平的 PAI-1 会导致血栓形成的环境,并导致更早和更严重的血管疾病。目前的证据还表明,PAI-1 具有昼夜节律波动的节律特征,在一天内的早晨有一个相位高峰,这可能解释了心血管事件高发的早晨。因此,PAI-1 是一个可能的药物靶点。尽管已经开发出几种 PAI-1 抑制剂,但尚无一种被允许用于临床使用。对节律的研究也导致了“时间治疗学”的概念,这是一种基于节律的药物治疗方案,有望改善糖尿病患者心血管并发症的治疗。在此,我们搜索了几个数据库并回顾了相关文章,以描述 PAI-1 的昼夜节律特征和内源性分子机制,它与胰岛素抵抗的关系,PAI-1 引起心血管并发症的原因,以及 PAI-1 抑制剂的当前发展。我们还总结了利用 PAI-1 的昼夜节律治疗糖尿病患者心血管并发症的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/782e/10067678/e76a4daf8169/fendo-14-1124353-g001.jpg

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