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衰老对阻力动脉的功能、结构和蛋白质组学影响

Functional, Structural and Proteomic Effects of Ageing in Resistance Arteries.

作者信息

Jensen Lars Jørn

机构信息

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Frederiksberg C, Denmark.

出版信息

Int J Mol Sci. 2024 Feb 23;25(5):2601. doi: 10.3390/ijms25052601.

Abstract

The normal ageing process affects resistance arteries, leading to various functional and structural changes. Systolic hypertension is a common occurrence in human ageing, and it is associated with large artery stiffening, heightened pulsatility, small artery remodeling, and damage to critical microvascular structures. Starting from young adulthood, a progressive elevation in the mean arterial pressure is evidenced by clinical and epidemiological data as well as findings from animal models. The myogenic response, a protective mechanism for the microcirculation, may face disruptions during ageing. The dysregulation of calcium entry channels (L-type, T-type, and TRP channels), dysfunction in intracellular calcium storage and extrusion mechanisms, altered expression of potassium channels, and a change in smooth muscle calcium sensitization may contribute to the age-related dysregulation of myogenic tone. Flow-mediated vasodilation, a hallmark of endothelial function, is compromised in ageing. This endothelial dysfunction is related to increased oxidative stress, lower nitric oxide bioavailability, and a low-grade inflammatory response, further exacerbating vascular dysfunction. Resistance artery remodeling in ageing emerges as a hypertrophic response of the vessel wall that is typically observed in conjunction with outward remodeling (in normotension), or as inward hypertrophic remodeling (in hypertension). The remodeling process involves oxidative stress, inflammation, reorganization of actin cytoskeletal components, and extracellular matrix fiber proteins. Reactive oxygen species (ROS) signaling and chronic low-grade inflammation play substantial roles in age-related vascular dysfunction. Due to its role in the regulation of vascular tone and structural proteins, the RhoA/Rho-kinase pathway is an important target in age-related vascular dysfunction and diseases. Understanding the intricate interplay of these factors is crucial for developing targeted interventions to mitigate the consequences of ageing on resistance arteries and enhance the overall vascular health.

摘要

正常衰老过程会影响阻力动脉,导致各种功能和结构变化。收缩期高血压在人类衰老过程中很常见,它与大动脉僵硬、搏动性增强、小动脉重塑以及关键微血管结构损伤有关。从青年期开始,临床和流行病学数据以及动物模型研究结果均表明平均动脉压会逐渐升高。肌源性反应作为微循环的一种保护机制,在衰老过程中可能会受到破坏。钙通道(L型、T型和瞬时受体电位通道)的失调、细胞内钙储存和外排机制的功能障碍、钾通道表达的改变以及平滑肌钙敏感性的变化,可能导致与年龄相关的肌源性张力失调。血流介导的血管舒张作为内皮功能的一个标志,在衰老过程中会受到损害。这种内皮功能障碍与氧化应激增加、一氧化氮生物利用度降低以及低度炎症反应有关,进一步加剧了血管功能障碍。衰老过程中的阻力动脉重塑表现为血管壁的肥厚反应,通常与向外重塑(在血压正常时)或向内肥厚性重塑(在高血压时)同时出现。重塑过程涉及氧化应激、炎症、肌动蛋白细胞骨架成分的重组以及细胞外基质纤维蛋白。活性氧(ROS)信号传导和慢性低度炎症在与年龄相关的血管功能障碍中起重要作用。由于RhoA/Rho激酶途径在调节血管张力和结构蛋白方面的作用,它是与年龄相关的血管功能障碍和疾病的一个重要靶点。了解这些因素之间复杂的相互作用对于制定有针对性的干预措施以减轻衰老对阻力动脉的影响并增强整体血管健康至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f930/10932216/9e9609c0ad03/ijms-25-02601-g001.jpg

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