Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing.

Autor: Thapa D; Section of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King's College London, London, United Kingdom., Valente JS; Section of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King's College London, London, United Kingdom., Barrett B; Section of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King's College London, London, United Kingdom., Smith MJ; Section of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King's College London, London, United Kingdom., Argunhan F; Section of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King's College London, London, United Kingdom., Lee SY; Section of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King's College London, London, United Kingdom.; Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, United Kingdom., Nikitochkina S; Section of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King's College London, London, United Kingdom., Kodji X; Section of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King's College London, London, United Kingdom.; Skin Research Institute, Agency of Science, Technology, and Research (A*STAR), Singapore, Singapore., Brain SD; Section of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King's College London, London, United Kingdom.
Jazyk: angličtina
Zdroj: ELife [Elife] 2021 Nov 02; Vol. 10. Date of Electronic Publication: 2021 Nov 02.
DOI: 10.7554/eLife.70153
Abstrakt: Ageing is associated with increased vulnerability to environmental cold exposure. Previously, we identified the role of the cold-sensitive transient receptor potential (TRP) A1, M8 receptors as vascular cold sensors in mouse skin. We hypothesised that this dynamic cold-sensor system may become dysfunctional in ageing. We show that behavioural and vascular responses to skin local environmental cooling are impaired with even moderate ageing, with reduced TRPM8 gene/protein expression especially. Pharmacological blockade of the residual TRPA1/TRPM8 component substantially diminished the response in aged, compared with young mice. This implies the reliance of the already reduced cold-induced vascular response in ageing mice on remaining TRP receptor activity. Moreover, sympathetic-induced vasoconstriction was reduced with downregulation of the α 2c adrenoceptor expression in ageing. The cold-induced vascular response is important for sensing cold and retaining body heat and health. These findings reveal that cold sensors, essential for this neurovascular pathway, decline as ageing onsets.
Competing Interests: DT, JV, BB, MS, FA, SL, SN, XK, SB No competing interests declared
(© 2021, Thapa et al.)
Databáze: MEDLINE
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