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探索衰老小鼠的主动脉僵硬度:全面的方法学概述。

Exploring aortic stiffness in aging mice: a comprehensive methodological overview.

作者信息

Vanalderwiert Laetitia, Henry Auberi, de Souza E Silva Juliana Martins, Carvajal-Berrio Daniel, Debelle Laurent, Wahart Amandine, Marzi Julia, Schenke-Layland Katja, Faury Gilles, Six Isabelle, Schmelzer Christian E H, Brinckmann Jürgen, Steenbock Heiko, Almagro Sébastien, Delacoux Frédéric, Jaisson Stéphane, Gillery Philippe, Maurice Pascal, Sartelet Hervé, Bennasroune Amar, Duca Laurent, Romier Béatrice, Blaise Sébastien

机构信息

UMR CNRS 7369 MEDyC, University of Reims Champagne-Ardenne, Reims 51100, France.

Fraunhofer Institute for Microstructure of Materials and Systems IMWS, Halle (Saale) 06120, Germany.

出版信息

Aging (Albany NY). 2024 Dec 2;17(2):280-307. doi: 10.18632/aging.206168.

Abstract

Stiffening of the vascular network is associated with the early stages of vascular aging, leading to cardiovascular disorders (hypertension), renal failures, or neurodegenerative diseases (Alzheimer's). Unfortunately, many people remain undiagnosed because diagnostic methods are either unsuitable for a large population or unfamiliar to clinicians which favor the hypertension evaluation. In preclinical research, stiffness studies are often partially conducted. We think that the evaluation of aortic stiffness is essential as it would improve our understanding of aging diseases progression. We propose here a systematic method using decision trees in a multi-scale and multimodal approaches. Our method was evaluated by analyzing the aortic situation in old and young mice. We demonstrate that both the endothelial and smooth muscle cells exhibit pronounced functional alterations in favor of constriction. Additionally, there is significant remodeling of the extracellular matrix, leading to a drastic degradation of elastic fibers and the accumulation of collagen in the aortic wall. This series of changes contributes to the development of vascular rigidity, a preliminary stage of arterial hypertension. Our results suggest that our method should improve preclinical understanding and encourage clinicians to equip themselves with tools for assessing vascular function, as it is an essential issue for preventing numerous pathologies.

摘要

血管网络的硬化与血管衰老的早期阶段相关,会导致心血管疾病(高血压)、肾衰竭或神经退行性疾病(阿尔茨海默病)。不幸的是,许多人仍未得到诊断,因为诊断方法要么不适用于大量人群,要么临床医生不熟悉,而这些方法更有利于高血压评估。在临床前研究中,硬度研究往往只是部分进行。我们认为评估主动脉硬度至关重要,因为这将增进我们对衰老疾病进展的理解。我们在此提出一种在多尺度和多模态方法中使用决策树的系统方法。我们的方法通过分析老年和年轻小鼠的主动脉状况进行评估。我们证明,内皮细胞和平滑肌细胞均表现出明显的功能改变,有利于收缩。此外,细胞外基质有显著重塑,导致弹性纤维急剧降解以及主动脉壁中胶原蛋白积累。这一系列变化促成了血管僵硬的发展,而血管僵硬是动脉高血压的一个初步阶段。我们的结果表明,我们的方法应能改善临床前的理解,并鼓励临床医生配备评估血管功能的工具,因为这是预防众多疾病的一个关键问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a91e/11892926/6b7a551afc60/aging-17-206168-g001.jpg

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