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Asic3 is a neuronal mechanosensor for pressure-induced vasodilation that protects against pressure ulcers

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Abstract

Pressure-induced vasodilation (PIV) delays the decrease in cutaneous blood flow produced by local application of low pressure to the skin, a physiologically appropriate adjustment of local vasomotor function. Individuals without a normal PIV response have a high risk of ulceration. Here we demonstrate that acid-sensing ion channel 3 (Asic3) is an essential neuronal sensor for the vasodilation response to direct pressure in both humans and rodents and for protecting against pressure ulcers in mice.

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Figure 1: Asic3 mediates the PIV response after local application of low pressures to the skin.
Figure 2: The ischemic response to compression is exacerbated by Asic3 deficiency.

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Acknowledgements

We would like to thank the subjects who participated in this study. We thank C. Viart-Ferber, A. Josset-Lamaugarny, G. James and N. Plèche (AnexPeau facility, Lyon) for helpful assistance in human and rodent studies. We are very grateful to S. Diochot and E. Deval (CNRS UMR 7275) for providing APETx2 and knockout mice, to P. Inquimbert, V. Friend (CNRS UMR 7275) and N. Gadot (Anipath facility, Lyon) for histological studies, and to R. Buttin and D. Katz for technical support for Perimed equipment. We also thank Fondation pour la Recherche Médicale and Prevention Education Recherche Soins Escarres for financial support.

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Author notes

  1. Jean Louis Saumet and Michel Lazdunski: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut de Biologie et Chimie des Protéines, Centre National de la Recherche Scientifique (CNRS) FRE 3310, Lyon, France

    Bérengère Fromy, Dominique Sigaudo-Roussel & Jean Louis Saumet

  2. Université de Lyon 1, FRE 3310, Lyon, France

    Bérengère Fromy, Dominique Sigaudo-Roussel & Jean Louis Saumet

  3. Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, UMR 7275, Valbonne, France

    Eric Lingueglia & Michel Lazdunski

  4. Université de Nice-Sophia Antipolis, UMR 7275, Valbonne, France

    Eric Lingueglia & Michel Lazdunski

  5. LabEx ICST, Valbonne, France

    Eric Lingueglia

Authors
  1. Bérengère Fromy
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  2. Eric Lingueglia
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  3. Dominique Sigaudo-Roussel
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  4. Jean Louis Saumet
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  5. Michel Lazdunski
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Contributions

B.F., J.L.S. and M.L. conceived of and designed the experiments, analyzed the data, and contributed to writing and editing the manuscript; B.F. performed the experiments; E.L. and D.S.-R. contributed to discussions and provided tools important for completion of the work.

Corresponding authors

Correspondence to Jean Louis Saumet or Michel Lazdunski.

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The authors declare no competing financial interests.

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Supplementry Figures 1–7 and Supplementary Methods (PDF 679 kb)

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Fromy, B., Lingueglia, E., Sigaudo-Roussel, D. et al. Asic3 is a neuronal mechanosensor for pressure-induced vasodilation that protects against pressure ulcers. Nat Med 18, 1205–1207 (2012). https://doi.org/10.1038/nm.2844

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  • DOI: https://doi.org/10.1038/nm.2844

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