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活性氧诱导的心力衰竭发病机制途径及潜在治疗策略

Reactive Oxygen Species Induced Pathways in Heart Failure Pathogenesis and Potential Therapeutic Strategies.

作者信息

Mongirdienė Aušra, Skrodenis Laurynas, Varoneckaitė Leila, Mierkytė Gerda, Gerulis Justinas

机构信息

Department of Biochemistry, Medical Academy, Lithuanian University of Health Sciences, Eiveniu str. 4, LT-50161 Kaunas, Lithuania.

Medical Academy, Lithuanian University of Health Sciences, Mickevičiaus str. 9, LT-44307 Kaunas, Lithuania.

出版信息

Biomedicines. 2022 Mar 3;10(3):602. doi: 10.3390/biomedicines10030602.

Abstract

With respect to structural and functional cardiac disorders, heart failure (HF) is divided into HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Oxidative stress contributes to the development of both HFrEF and HFpEF. Identification of a broad spectrum of reactive oxygen species (ROS)-induced pathways in preclinical models has provided new insights about the importance of ROS in HFrEF and HFpEF development. While current treatment strategies mostly concern neuroendocrine inhibition, recent data on ROS-induced metabolic pathways in cardiomyocytes may offer additional treatment strategies and targets for both of the HF forms. The purpose of this article is to summarize the results achieved in the fields of: (1) ROS importance in HFrEF and HFpEF pathophysiology, and (2) treatments for inhibiting ROS-induced pathways in HFrEF and HFpEF patients. ROS-producing pathways in cardiomyocytes, ROS-activated pathways in different HF forms, and treatment options to inhibit their action are also discussed.

摘要

关于心脏结构和功能紊乱,心力衰竭(HF)分为射血分数降低的心力衰竭(HFrEF)和射血分数保留的心力衰竭(HFpEF)。氧化应激在HFrEF和HFpEF的发展中均起作用。在临床前模型中对广泛的活性氧(ROS)诱导途径的鉴定,为ROS在HFrEF和HFpEF发展中的重要性提供了新的见解。虽然目前的治疗策略主要涉及神经内分泌抑制,但最近关于ROS诱导的心肌细胞代谢途径的数据可能为这两种心力衰竭形式提供额外的治疗策略和靶点。本文的目的是总结在以下领域取得的成果:(1)ROS在HFrEF和HFpEF病理生理学中的重要性,以及(2)针对HFrEF和HFpEF患者抑制ROS诱导途径的治疗方法。还讨论了心肌细胞中的ROS产生途径、不同心力衰竭形式中的ROS激活途径以及抑制其作用的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0afe/8945343/20c6cba6e79b/biomedicines-10-00602-g001.jpg

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