Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity
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
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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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 1

Endothelial Piezo1 determines physical performance but not desire for activity.

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Endothelial Piezo1 determines physical performance but not desire for ac...
Throughout the figure, data in gray represent control mice (Ctrl) and data in orange are for Piezo1ΔEC mice. The lighter color is for data sampled during the light cycle (inactive period) and darker color for data during the dark cycle (active period). (A) Pooled and averaged ambulatory activity (XAMB) across 3 light and dark cycles for Ctrl mice and Piezo1ΔEC mice. (B) Day-by-day averaged ambulatory activity. (C) Similar to A but showing exploratory activity (ZTOT). (D) Day-by-day averaged exploratory activity. (E) Similar to A but showing running wheel rotation counts (voluntary activity). (F) Day-by-day averaged voluntary activity. (G) Cumulative running wheel rotations during 72-hour recording. Gray shaded areas indicate the dark cycles. (H) Number of active bouts of exercise (periods of activity defined as activity seen in 1 or more consecutive 10-minute intervals). (I) Number of interbout pauses (periods of inactivity between 2 bouts of exercise). (J) Percentage of time for which mice were active on the wheel. (K) Percentage of time for which mice were off the wheel (inactive time). (L) Normalization of running wheel rotations per active bouts of exercise. (M) Running-wheel speed. All data are for n = 10 mice per group (mean ± SD). Superimposed dots are the individual underlying data values for each individual mouse. **P < 0.01, ***P < 0.001 vs. light cycle; #P < 0.05, ##P < 0.01, ###P < 0.001 vs. Ctrl mice. Statistical significance was evaluated using 2-way ANOVA followed by Tukey’s HSD post hoc test for multiple comparisons.