脑血管内皮功能障碍:BACE1 的作用

IF 7.4 1区 医学 Q1 HEMATOLOGY Arteriosclerosis, Thrombosis, and Vascular Biology Pub Date : 2024-08-01 Epub Date: 2024-06-13 DOI:10.1161/ATVBAHA.124.320798
Zvonimir S Katusic, Livius V d'Uscio, Tongrong He
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引用次数: 0

摘要

人们日益认识到,内皮功能失调是心血管风险因素与痴呆症(包括阿尔茨海默病)之间的机理联系。BACE1(β位淀粉样-β前体蛋白裂解酶1)负责对APP(淀粉样-β前体蛋白)进行β处理,这是产生Aβ(淀粉样-β)肽的第一步,而Aβ肽是阿尔茨海默病发病机制中的罪魁祸首。在病理条件下,BACE1 的过度激活会通过 Aβ 依赖性和 Aβ 非依赖性机制对内皮功能产生有害影响。脑血管中 Aβ 的局部高浓度是导致内皮细胞丧失主要血管保护功能的原因。最近的研究发现,内皮细胞 BACE1 的 Aβ 依赖性蛋白水解活性对内皮细胞功能障碍的发病机制有重要作用。本综述批判性地评估了支持以下概念的现有证据,即脑血管内皮中表达的 BACE1 过度激活会损害脑血管的关键平衡功能。这一概念具有重要的治疗意义。事实上,提高对内皮功能障碍机制的认识可能有助于开发保护和维持脑血管健康功能的新方法。
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Cerebrovascular Endothelial Dysfunction: Role of BACE1.

Dysfunctional endothelium is increasingly recognized as a mechanistic link between cardiovascular risk factors and dementia, including Alzheimer disease. BACE1 (β-site amyloid-β precursor protein-cleaving enzyme 1) is responsible for β-processing of APP (amyloid-β precursor protein), the first step in the production of Aβ (amyloid-β) peptides, major culprits in the pathogenesis of Alzheimer disease. Under pathological conditions, excessive activation of BACE1 exerts detrimental effects on endothelial function by Aβ-dependent and Aβ-independent mechanisms. High local concentration of Aβ in the brain blood vessels is responsible for the loss of key vascular protective functions of endothelial cells. More recent studies recognized significant contribution of Aβ-independent proteolytic activity of endothelial BACE1 to the pathogenesis of endothelial dysfunction. This review critically evaluates existing evidence supporting the concept that excessive activation of BACE1 expressed in the cerebrovascular endothelium impairs key homeostatic functions of the brain blood vessels. This concept has important therapeutic implications. Indeed, improved understanding of the mechanisms of endothelial dysfunction may help in efforts to develop new approaches to the protection and preservation of healthy cerebrovascular function.

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来源期刊
CiteScore
15.60
自引率
2.30%
发文量
337
审稿时长
2-4 weeks
期刊介绍: The journal "Arteriosclerosis, Thrombosis, and Vascular Biology" (ATVB) is a scientific publication that focuses on the fields of vascular biology, atherosclerosis, and thrombosis. It is a peer-reviewed journal that publishes original research articles, reviews, and other scholarly content related to these areas. The journal is published by the American Heart Association (AHA) and the American Stroke Association (ASA). The journal was published bi-monthly until January 1992, after which it transitioned to a monthly publication schedule. The journal is aimed at a professional audience, including academic cardiologists, vascular biologists, physiologists, pharmacologists and hematologists.
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