Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity
Fiona Bartoli, … , Lee D. Roberts, David J. Beech
Fiona Bartoli, … , Lee D. Roberts, David J. Beech
Published January 13, 2022
Citation Information: J Clin Invest. 2022;132(5):e141775. https://doi.org/10.1172/JCI141775.
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Research Article Muscle biology Vascular biology

Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity

Abstract

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.

Authors

Fiona Bartoli, Marjolaine Debant, Eulashini Chuntharpursat-Bon, Elizabeth L. Evans, Katie E. Musialowski, Gregory Parsonage, Lara C. Morley, T. Simon Futers, Piruthivi Sukumar, T. Scott Bowen, Mark T. Kearney, Laeticia Lichtenstein, Lee D. Roberts, David J. Beech

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Figure 2

Endothelial Piezo1 specifically affects microvascular density.

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Endothelial Piezo1 specifically affects microvascular density. (A) Immun...
(A) Immunohistochemistry of gastrocnemius muscle cross sections for myosin heavy chain (MHC) type 2a (green) plus type 2b (red, left) or type 2x (magenta, right). Scale bars: 100 μm. (B) Quantification of the relative frequency of the different fiber types in gastrocnemius muscle. (C) Immunohistochemistry for CD31 (red) to visualize endothelial cells in capillaries of gastrocnemius muscle sections. Scale bars: 50 μm. (D) Mean data for capillary density measured from images of the type shown in C. (E) Similar to D but showing mean data for the ratio of capillaries to muscle fibers. (F) Immunohistochemistry for isolectin B4 (IB4, green) to visualize endothelial cells in capillaries of gastrocnemius muscle sections. Scale bars: 50 μm. (G) Mean data for capillary density measured from images of the type shown in F. (H) Similar to G but showing mean data for the ratio of capillaries to muscle fibers. All data are for n = 7 to 8 mice per group (mean ± SD). Superimposed dots are the underlying data values for each individual mouse. Gray indicates muscles from Ctrl mice and green indicates muscles from Piezo1ΔEC mice. ##P < 0.01, ###P < 0.001 vs. ctrl mice. Statistical significance was evaluated using Student’s t test.