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间质干细胞输注可使阻塞性呼吸暂停引起的主动脉重构恢复正常。

Aortic remodelling induced by obstructive apneas is normalized with mesenchymal stem cells infusion.

机构信息

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.

出版信息

Sci Rep. 2019 Aug 7;9(1):11443. doi: 10.1038/s41598-019-47813-1.

Abstract

Obstructive sleep apnea syndrome (OSA) promotes aortic dilatation, increased stiffness and accelerated atherosclerosis, but the mechanisms of vascular remodelling are not known. We aimed to assess vascular remodelling, its mechanisms, and the effect of mesenchymal stem cells (MSC) infusions in a clinically relevant rat model of chronic OSA involving recurrent airway obstructions leading thoracic pressure swings and intermittent hypoxia/hypercapnia (OSA-rats). Another group of rats were placed in the same setup without air obstructions (Sham-rats) and were considered controls. Our study demonstrates that chronic, non-invasive repetitive airway obstructions mimicking OSA promote remarkable structural changes of the descending thoracic aorta such as eccentric aortic hypertrophy due to an increased wall thickness and lumen diameter, an increase in the number of elastin fibers which, in contrast, get ruptured, but no changes in tunica media fibrosis. As putative molecular mechanisms of the OSA-induced vascular changes we identified an increase in reactive oxygen species and renin-angiotensin system markers and an imbalance in oxide nitric synthesis. Our results also indicate that MSC infusion blunts the OSA-related vascular changes, most probably due to their anti-inflammatory properties.

摘要

阻塞性睡眠呼吸暂停综合征(OSA)可导致主动脉扩张、僵硬度增加和动脉粥样硬化加速,但血管重构的机制尚不清楚。我们旨在评估血管重构及其机制,并评估间充质干细胞(MSC)输注在涉及反复气道阻塞导致胸压波动和间歇性低氧/高碳酸血症的慢性 OSA 临床相关大鼠模型中的作用(OSA-大鼠)。另一组大鼠在没有气道阻塞的情况下置于相同设置中(假手术大鼠),并被认为是对照组。我们的研究表明,模拟 OSA 的慢性、非侵入性、反复性气道阻塞会导致降主动脉发生显著的结构变化,例如由于壁厚和管腔直径增加导致的偏心性主动脉肥厚、弹性纤维数量增加,而弹性纤维断裂,但中膜纤维化没有变化。作为 OSA 引起的血管变化的潜在分子机制,我们发现活性氧和肾素-血管紧张素系统标志物增加,以及氧化氮合成失衡。我们的结果还表明,MSC 输注可减轻与 OSA 相关的血管变化,这可能归因于其抗炎特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81c0/6685984/97663879eab1/41598_2019_47813_Fig1_HTML.jpg

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