鞘脂类介导的细胞信号在高血糖、急性心肌梗死和心力衰竭相互作用中的潜在作用。

The potential role of sphingolipid-mediated cell signaling in the interaction between hyperglycemia, acute myocardial infarction and heart failure.

机构信息

University of Hull, Hull and East Yorkshire Hospitals NHS Trust, Academic Cardiology, Hull, East Yorkshire HU16 5JQ, UK.

出版信息

Expert Opin Ther Targets. 2012 Aug;16(8):791-800. doi: 10.1517/14728222.2012.699043. Epub 2012 Jul 5.

Abstract

INTRODUCTION

Patients with acute myocardial infarction or heart failure frequently have abnormalities of glucose metabolism and insulin resistance, both of which are associated with a poor outcome. Sphingolipids are a class of lipids, which play important roles in cellular biological processes including insulin resistance and myocardial ischemia.

AREAS COVERED

This review examines the available evidence linking abnormalities in sphingolipids, glucose tolerance and insulin resistance to acute myocardial infarction and heart failure.

EXPERT OPINION

Pharmacological and genetic activation of enzymes controlling key sphingolipids synthesis, such as sphingosine-1-phosphate, increases insulin sensitivity in rodents and increases myocardial tolerance to ischemia. Major projects are being realized to develop clinical strategies to manipulate sphingolipid metabolism in this clinical settings, with the ultimate goal of increasing insulin sensitivity and augmenting myocardial tolerance to ischemia. Thus, a clear understanding of the sphingolipid-mediated signaling in ischemic heart disease is required to devise strategies to develop novel agents and technologies that directly target this signaling pathway.

摘要

简介

急性心肌梗死或心力衰竭患者常伴有葡萄糖代谢异常和胰岛素抵抗,两者均与预后不良有关。鞘脂是一类脂质,在包括胰岛素抵抗和心肌缺血在内的细胞生物学过程中发挥重要作用。

涵盖领域

本文综述了现有的关于鞘脂异常、葡萄糖耐量和胰岛素抵抗与急性心肌梗死和心力衰竭之间关系的证据。

专家意见

在啮齿动物中,控制关键鞘脂合成的酶(如 1-磷酸鞘氨醇)的药理学和遗传学激活可增加胰岛素敏感性,并增加心肌对缺血的耐受。目前正在开展重大项目,以制定在这些临床环境中操纵鞘脂代谢的临床策略,最终目标是提高胰岛素敏感性和增强心肌对缺血的耐受。因此,需要明确了解缺血性心脏病中鞘脂介导的信号转导,以制定策略来开发直接靶向该信号通路的新型药物和技术。

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