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Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity
The Journal of Clinical Investigation ( IF 13.3 ) Pub Date : 2022 , DOI: 10.1172/jci141775
Fiona Bartoli 1 , Marjolaine Debant 1 , Eulashini Chuntharpursat-Bon 1 , Elizabeth L Evans 1 , Katie E Musialowski 1 , Gregory Parsonage 1 , Lara C Morley 1 , T Simon Futers 1 , Piruthivi Sukumar 1 , T Scott Bowen 2 , Mark T Kearney 1 , Laeticia Lichtenstein 1 , Lee D Roberts 1 , David J Beech 1
Affiliation  

Piezo1 forms mechanically activated nonselective cation channels that contribute to endothelial response to fluid flow. Here we reveal an important role in the control of capillary density. Conditional endothelial cell–specific deletion of Piezo1 in adult mice depressed physical performance. Muscle microvascular endothelial cell apoptosis and capillary rarefaction were evident and sufficient to account for the effect on performance. There was selective upregulation of thrombospondin-2 (TSP2), an inducer of endothelial cell apoptosis, with no effect on TSP1, a related important player in muscle physiology. TSP2 was poorly expressed in muscle endothelial cells but robustly expressed in muscle pericytes, in which nitric oxide (NO) repressed the Tsp2 gene without an effect on Tsp1. In endothelial cells, Piezo1 was required for normal expression of endothelial NO synthase. The data suggest an endothelial cell–pericyte partnership of muscle in which endothelial Piezo1 senses blood flow to sustain capillary density and thereby maintain physical capability.

中文翻译:

内皮 Piezo1 维持肌肉毛细血管密度并有助于身体活动

Piezo1 形成机械激活的非选择性阳离子通道,有助于内皮对流体流动的反应。在这里,我们揭示了在控制毛细血管密度中的重要作用。成年小鼠中 Piezo1 的条件性内皮细胞特异性缺失会降低身体机能。肌肉微血管内皮细胞凋亡和毛细血管稀疏是明显的,足以解释对性能的影响。血小板反应蛋白 2 (TSP2) 是一种内皮细胞凋亡诱导剂,它有选择性上调,但对 TSP1 没有影响,TSP1 是肌肉生理学中相关的重要参与者。TSP2 在肌肉内皮细胞中表达不佳,但在肌肉周细胞中表达强烈,其中一氧化氮 (NO) 抑制Tsp2基因而不影响Tsp1. 在内皮细胞中,Piezo1 是内皮 NO 合酶正常表达所必需的。数据表明肌肉的内皮细胞-周细胞伙伴关系,其中内皮 Piezo1 感知血流以维持毛细血管密度,从而维持身体能力。
更新日期:2022-03-01
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