Inhibition of transient receptor potential cation channel 6 promotes capillary arterialization during post-ischaemic blood flow recovery

Abstract: Background and Purpose: Capillary arterialization, characterized by the coverage of pre-existing or nascent capillary vessels with vascular smooth muscle cells (VSMCs), is critical for the development of collateral arterioles to improve post-ischaemic blood flow. We previously demonstra...

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Detalles Bibliográficos
Autores principales: Numaga-Tomita, Takuro, Shimauchi, Tsukasa, Kato, Yuri, Nishiyama, Kazuhiro, Nishimura, Akiyuki, Sakata, Kosuke, Inada, Hiroyuki, Kita, Satomi, Iwamoto, Takahiro, Nabekura, Junichi, Birnbaumer, Lutz, Mori, Yasuo, Nishida, Motohiro
Formato: Artículo
Lenguaje:Inglés
Publicado: Wiley 2022
Materias:
TRPC6
ENFERMEDAD ATEROSCLEROTICA
RECEPTORES
CÉLULA MUSCULAR LISA VASCULAR
FOSFORILACIÓN
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/15358
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-15358
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic TRPC6
ENFERMEDAD ATEROSCLEROTICA
RECEPTORES
CÉLULA MUSCULAR LISA VASCULAR
FOSFORILACIÓN
spellingShingle TRPC6
ENFERMEDAD ATEROSCLEROTICA
RECEPTORES
CÉLULA MUSCULAR LISA VASCULAR
FOSFORILACIÓN
Numaga-Tomita, Takuro
Shimauchi, Tsukasa
Kato, Yuri
Nishiyama, Kazuhiro
Nishimura, Akiyuki
Sakata, Kosuke
Inada, Hiroyuki
Kita, Satomi
Iwamoto, Takahiro
Nabekura, Junichi
Birnbaumer, Lutz
Mori, Yasuo
Nishida, Motohiro
Inhibition of transient receptor potential cation channel 6 promotes capillary arterialization during post-ischaemic blood flow recovery
topic_facet TRPC6
ENFERMEDAD ATEROSCLEROTICA
RECEPTORES
CÉLULA MUSCULAR LISA VASCULAR
FOSFORILACIÓN
description Abstract: Background and Purpose: Capillary arterialization, characterized by the coverage of pre-existing or nascent capillary vessels with vascular smooth muscle cells (VSMCs), is critical for the development of collateral arterioles to improve post-ischaemic blood flow. We previously demonstrated that the inhibition of transient receptor potential 6 subfamily C, member 6 (TRPC6) channels facilitate contractile differentiation of VSMCs under ischaemic stress. We here investigated whether TRPC6 inhibition promotes post-ischaemic blood flow recovery through capillary arterialization in vivo. Experimental Approach: Mice were subjected to hindlimb ischaemia by ligating left femoral artery. The recovery rate of peripheral blood flow was calculated by the ratio of ischaemic left leg to non-ischaemic right one. The number and diameter of blood vessels were analysed by immunohistochemistry. Expression and phosphorylation levels of TRPC6 proteins were determined by western blotting and immunohistochemistry. Key Results: Although the post-ischaemic blood flow recovery is reportedly dependent on endothelium-dependent relaxing factors, systemic TRPC6 deletion significantly promoted blood flow recovery under the condition that nitric oxide or prostacyclin production were inhibited, accompanying capillary arterialization. Cilostazol, a clinically approved drug for peripheral arterial disease, facilitates blood flow recovery by inactivating TRPC6 via phosphorylation at Thr69 in VSMCs. Furthermore, inhibition of TRPC6 channel activity by pyrazole-2 (Pyr2; BTP2; YM-58483) promoted post-ischaemic blood flow recovery in Apolipoprotein E-knockout mice. Conclusion and Implications: Suppression of TRPC6 channel activity in VSMCs could be a new strategy for the improvement of post-ischaemic peripheral blood circulation.
format Artículo
author Numaga-Tomita, Takuro
Shimauchi, Tsukasa
Kato, Yuri
Nishiyama, Kazuhiro
Nishimura, Akiyuki
Sakata, Kosuke
Inada, Hiroyuki
Kita, Satomi
Iwamoto, Takahiro
Nabekura, Junichi
Birnbaumer, Lutz
Mori, Yasuo
Nishida, Motohiro
author_facet Numaga-Tomita, Takuro
Shimauchi, Tsukasa
Kato, Yuri
Nishiyama, Kazuhiro
Nishimura, Akiyuki
Sakata, Kosuke
Inada, Hiroyuki
Kita, Satomi
Iwamoto, Takahiro
Nabekura, Junichi
Birnbaumer, Lutz
Mori, Yasuo
Nishida, Motohiro
author_sort Numaga-Tomita, Takuro
title Inhibition of transient receptor potential cation channel 6 promotes capillary arterialization during post-ischaemic blood flow recovery
title_short Inhibition of transient receptor potential cation channel 6 promotes capillary arterialization during post-ischaemic blood flow recovery
title_full Inhibition of transient receptor potential cation channel 6 promotes capillary arterialization during post-ischaemic blood flow recovery
title_fullStr Inhibition of transient receptor potential cation channel 6 promotes capillary arterialization during post-ischaemic blood flow recovery
title_full_unstemmed Inhibition of transient receptor potential cation channel 6 promotes capillary arterialization during post-ischaemic blood flow recovery
title_sort inhibition of transient receptor potential cation channel 6 promotes capillary arterialization during post-ischaemic blood flow recovery
publisher Wiley
publishDate 2022
url https://repositorio.uca.edu.ar/handle/123456789/15358
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