Canonical transient receptor potential 6 channel deficiency promotes smooth muscle cells dedifferentiation and increased proliferation after arterial injury

Abstract: Objective: Previous studies showed the benefit of canonical transient receptor potential 6 (TRPC6) channel deficiency in promoting endothelial healing of arterial injuries in hypercholesterolemic animals. Long-term studies utilizing a carotid wire-injury model were undertaken in wild-type...

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Autores principales: Smith, Andrew H., Putta, Priya, Driscoll, Erin C., Chaudhuri, Pinaki, Birnbaumer, Lutz, Rosenbaum, Michael A., Graham, Linda M.
Formato: Artículo
Lenguaje:Inglés
Publicado: Elsevier 2021
Materias:
TRPC6
LESIONES
TECNICAS QUIRURGICAS
SISTEMA CARDIOVASCULAR
GENES
PROTEINAS
CELULAS
FISIOPATOLOGÍA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/11623
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-11623
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
LESIONES
TECNICAS QUIRURGICAS
SISTEMA CARDIOVASCULAR
GENES
PROTEINAS
CELULAS
FISIOPATOLOGÍA
spellingShingle TRPC6
LESIONES
TECNICAS QUIRURGICAS
SISTEMA CARDIOVASCULAR
GENES
PROTEINAS
CELULAS
FISIOPATOLOGÍA
Smith, Andrew H.
Putta, Priya
Driscoll, Erin C.
Chaudhuri, Pinaki
Birnbaumer, Lutz
Rosenbaum, Michael A.
Graham, Linda M.
Canonical transient receptor potential 6 channel deficiency promotes smooth muscle cells dedifferentiation and increased proliferation after arterial injury
topic_facet TRPC6
LESIONES
TECNICAS QUIRURGICAS
SISTEMA CARDIOVASCULAR
GENES
PROTEINAS
CELULAS
FISIOPATOLOGÍA
description Abstract: Objective: Previous studies showed the benefit of canonical transient receptor potential 6 (TRPC6) channel deficiency in promoting endothelial healing of arterial injuries in hypercholesterolemic animals. Long-term studies utilizing a carotid wire-injury model were undertaken in wild-type (WT) and TRPC6−/− mice to determine the effects of TRPC6 on phenotypic modulation of vascular smooth muscle cells (SMC) and neointimal hyperplasia. We hypothesized that TRPC6 was essential in the maintenance or reexpression of a differentiated SMC phenotype and minimized luminal stenosis following arterial injury. Methods: The common carotid arteries (CCA) of WT and TRPC6−/− mice were evaluated at baseline and 4 weeks after wire injury. At baseline, CCA of TRPC6−/− mice had reduced staining of MYH11 and SM22, fewer elastin lamina, luminal dilation, and wall thinning. After carotid wire injury, TRPC6−/− mice developed significantly more pronounced luminal stenosis compared with WT mice. Injured TRPC6−/− CCA demonstrated increased medial/intimal cell number and active cell proliferation when compared with WT CCA. Immunohistochemistry suggested that expression of contractile biomarkers in medial SMC were essentially at baseline levels in WT CCA at 28 days after wire injury. By contrast, at 28 days after injury medial SMC from TRPC6−/− CCA showed a significant decrease in the expression of contractile biomarkers relative to baseline levels. To assess the role of TRPC6 in systemic arterial SMC phenotype modulation, SMC were harvested from thoracic aortae of WT and TRPC6−/− mice and were characterized. TRPC6−/− SMC showed enhanced proliferation and migration in response to serum stimulation. Expression of contractile phenotype biomarkers, MYH11 and SM22, was attenuated in TRPC6−/− SMC. siRNA-mediated TRPC6 deficiency inhibited contractile biomarker expression in a mouse SMC line. Conclusions: These results suggest that TRPC6 contributes to the restoration or maintenance of arterial SMC contractile phenotype following injury. Understanding the role of TRPC6 in phenotypic modulation may lead to mechanism-based therapies for attenuation of IH.
format Artículo
author Smith, Andrew H.
Putta, Priya
Driscoll, Erin C.
Chaudhuri, Pinaki
Birnbaumer, Lutz
Rosenbaum, Michael A.
Graham, Linda M.
author_facet Smith, Andrew H.
Putta, Priya
Driscoll, Erin C.
Chaudhuri, Pinaki
Birnbaumer, Lutz
Rosenbaum, Michael A.
Graham, Linda M.
author_sort Smith, Andrew H.
title Canonical transient receptor potential 6 channel deficiency promotes smooth muscle cells dedifferentiation and increased proliferation after arterial injury
title_short Canonical transient receptor potential 6 channel deficiency promotes smooth muscle cells dedifferentiation and increased proliferation after arterial injury
title_full Canonical transient receptor potential 6 channel deficiency promotes smooth muscle cells dedifferentiation and increased proliferation after arterial injury
title_fullStr Canonical transient receptor potential 6 channel deficiency promotes smooth muscle cells dedifferentiation and increased proliferation after arterial injury
title_full_unstemmed Canonical transient receptor potential 6 channel deficiency promotes smooth muscle cells dedifferentiation and increased proliferation after arterial injury
title_sort canonical transient receptor potential 6 channel deficiency promotes smooth muscle cells dedifferentiation and increased proliferation after arterial injury
publisher Elsevier
publishDate 2021
url https://repositorio.uca.edu.ar/handle/123456789/11623
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