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LKB1:心血管疾病治疗的新兴靶点。

LKB1: An emerging therapeutic target for cardiovascular diseases.

机构信息

Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Tehran University of Medical Sciences, Iran.

出版信息

Life Sci. 2022 Oct 1;306:120844. doi: 10.1016/j.lfs.2022.120844. Epub 2022 Jul 27.

Abstract

Cardiovascular diseases (CVDs) are currently the most common cause of morbidity and mortality worldwide. Experimental studies suggest that liver kinase B1 (LKB1) plays an important role in the heart. Several studies have shown that cardiomyocyte-specific LKB1 deletion leads to hypertrophic cardiomyopathy, left ventricular contractile dysfunction, and an increased risk of atrial fibrillation. In addition, the cardioprotective effects of several medicines and natural compounds, including metformin, empagliflozin, bexarotene, and resveratrol, have been reported to be associated with LKB1 activity. LKB1 limits the size of the damaged myocardial area by modifying cellular metabolism, enhancing the antioxidant system, suppressing hypertrophic signals, and inducing mild autophagy, which are all primarily mediated by the AMP-activated protein kinase (AMPK) energy sensor. LKB1 also improves myocardial efficiency by modulating the function of contractile proteins, regulating the expression of electrical channels, and increasing vascular dilatation. Considering these properties, stimulation of LKB1 signaling offers a promising approach in the prevention and treatment of heart diseases.

摘要

心血管疾病(CVDs)是目前全球发病率和死亡率最高的疾病。实验研究表明,肝激酶 B1(LKB1)在心脏中发挥着重要作用。有几项研究表明,心肌细胞特异性 LKB1 缺失可导致肥厚型心肌病、左心室收缩功能障碍和房颤风险增加。此外,几种药物和天然化合物的心脏保护作用,包括二甲双胍、恩格列净、贝沙罗汀和白藜芦醇,已被报道与 LKB1 活性有关。LKB1 通过调节细胞代谢、增强抗氧化系统、抑制肥大信号和诱导轻度自噬来限制受损心肌区域的大小,所有这些主要都是由 AMP 激活的蛋白激酶(AMPK)能量传感器介导的。LKB1 还通过调节收缩蛋白的功能、调节电通道的表达和增加血管扩张来提高心肌效率。鉴于这些特性,刺激 LKB1 信号转导为预防和治疗心脏病提供了一种很有前途的方法。

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