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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| Autores principales: | , , , , , , , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
Wiley
2022
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| Materias: | |
| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/15358 |
| Aporte de: |
| Sumario: | 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. |
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