Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity.
Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity.
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内皮Piezo1维持肌肉毛细血管密度，有助于身体活动。
DOI：
10.1172/jci141775
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发表时间：
2022-03-01
期刊：
影响因子：
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通讯作者：
Beech DJ
中科院分区：
文献类型：
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作者：
Bartoli F;Debant M;Chuntharpursat-Bon E;Evans EL;Musialowski KE;Parsonage G;Morley LC;Futers TS;Sukumar P;Bowen TS;Kearney MT;Lichtenstein L;Roberts LD;Beech DJ
Piezo1形成机械激活的非选择性阳离子通道，有助于内皮细胞对流体流动的反应。在这里，我们揭示了在毛细管密度控制中的重要作用。成年小鼠内皮细胞特异性的Piezo1条件缺失会降低身体表现。肌肉微血管内皮细胞凋亡和毛细血管稀疏是明显的，足以说明对性能的影响。血栓反应蛋白-2 （TSP2）选择性上调，TSP2是内皮细胞凋亡的诱导剂，对TSP1没有影响，而TSP1在肌肉生理学中起重要作用。TSP2在肌肉内皮细胞中表达较差，但在肌肉周细胞中表达较强，其中一氧化氮（NO）抑制了TSP2基因，但对TSP2无影响。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。
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.