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Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE(-/-) Mice

Cathepsin K (catK) is a potent lysosomal cysteine protease involved in extracellular matrix (ECM) degradation and inflammatory remodeling responses. Here we have investigated the contribution of catK deficiency on carotid arterial remodeling in response to flow cessation in apoE(-/-) and wild type (...

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Autores principales: Donners, Marjo M. P. C., Bai, Lili, Lutgens, Suzanne P. M., Wijnands, Erwin, Johnson, Jason, Schurgers, Leon J., Liu, Cong-Lin, Daemen, Mat J. A. P., Cleutjens, Kitty B. J. M., Shi, Guo-Ping, Biessen, Erik A. L., Heeneman, Sylvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026377/
https://www.ncbi.nlm.nih.gov/pubmed/27636705
http://dx.doi.org/10.1371/journal.pone.0162595
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author Donners, Marjo M. P. C.
Bai, Lili
Lutgens, Suzanne P. M.
Wijnands, Erwin
Johnson, Jason
Schurgers, Leon J.
Liu, Cong-Lin
Daemen, Mat J. A. P.
Cleutjens, Kitty B. J. M.
Shi, Guo-Ping
Biessen, Erik A. L.
Heeneman, Sylvia
author_facet Donners, Marjo M. P. C.
Bai, Lili
Lutgens, Suzanne P. M.
Wijnands, Erwin
Johnson, Jason
Schurgers, Leon J.
Liu, Cong-Lin
Daemen, Mat J. A. P.
Cleutjens, Kitty B. J. M.
Shi, Guo-Ping
Biessen, Erik A. L.
Heeneman, Sylvia
author_sort Donners, Marjo M. P. C.
collection PubMed
description Cathepsin K (catK) is a potent lysosomal cysteine protease involved in extracellular matrix (ECM) degradation and inflammatory remodeling responses. Here we have investigated the contribution of catK deficiency on carotid arterial remodeling in response to flow cessation in apoE(-/-) and wild type (wt) background. Ligation-induced hyperplasia is considerably aggravated in apoE(-/-) versus wt mice. CatK protein expression was significantly increased in neointimal lesions of apoE(-/-) compared with wt mice, suggesting a role for catK in intimal hyperplasia under hyperlipidemic conditions. Surprisingly, CatK deficiency completely blunted the augmented hyperplastic response to flow cessation in apoE(-/-), whereas vascular remodeling in wt mice was unaffected. As catK deficiency did neither alter lesion collagen content and elastic laminae fragmentation in vivo, we focused on effects of catK on (systemic) inflammatory responses. CatK deficiency significantly reduced circulating CD3 T-cell numbers, but increased the regulatory T cell subset in apoE(-/-) but not wt mice. Moreover, catK deficiency changed CD11b+Ly6G-Ly6C (high) monocyte distribution in apoE(-/-) but not wt mice and tended to favour macrophage M2a polarization. In conclusion, catK deficiency almost completely blunted the increased vascular remodeling response of apoE(-/-) mice to flow cessation, possibly by correcting hyperlipidemia-associated pro-inflammatory effects on the peripheral immune response.
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spelling pubmed-50263772016-09-27 Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE(-/-) Mice Donners, Marjo M. P. C. Bai, Lili Lutgens, Suzanne P. M. Wijnands, Erwin Johnson, Jason Schurgers, Leon J. Liu, Cong-Lin Daemen, Mat J. A. P. Cleutjens, Kitty B. J. M. Shi, Guo-Ping Biessen, Erik A. L. Heeneman, Sylvia PLoS One Research Article Cathepsin K (catK) is a potent lysosomal cysteine protease involved in extracellular matrix (ECM) degradation and inflammatory remodeling responses. Here we have investigated the contribution of catK deficiency on carotid arterial remodeling in response to flow cessation in apoE(-/-) and wild type (wt) background. Ligation-induced hyperplasia is considerably aggravated in apoE(-/-) versus wt mice. CatK protein expression was significantly increased in neointimal lesions of apoE(-/-) compared with wt mice, suggesting a role for catK in intimal hyperplasia under hyperlipidemic conditions. Surprisingly, CatK deficiency completely blunted the augmented hyperplastic response to flow cessation in apoE(-/-), whereas vascular remodeling in wt mice was unaffected. As catK deficiency did neither alter lesion collagen content and elastic laminae fragmentation in vivo, we focused on effects of catK on (systemic) inflammatory responses. CatK deficiency significantly reduced circulating CD3 T-cell numbers, but increased the regulatory T cell subset in apoE(-/-) but not wt mice. Moreover, catK deficiency changed CD11b+Ly6G-Ly6C (high) monocyte distribution in apoE(-/-) but not wt mice and tended to favour macrophage M2a polarization. In conclusion, catK deficiency almost completely blunted the increased vascular remodeling response of apoE(-/-) mice to flow cessation, possibly by correcting hyperlipidemia-associated pro-inflammatory effects on the peripheral immune response. Public Library of Science 2016-09-16 /pmc/articles/PMC5026377/ /pubmed/27636705 http://dx.doi.org/10.1371/journal.pone.0162595 Text en © 2016 Donners et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Donners, Marjo M. P. C.
Bai, Lili
Lutgens, Suzanne P. M.
Wijnands, Erwin
Johnson, Jason
Schurgers, Leon J.
Liu, Cong-Lin
Daemen, Mat J. A. P.
Cleutjens, Kitty B. J. M.
Shi, Guo-Ping
Biessen, Erik A. L.
Heeneman, Sylvia
Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE(-/-) Mice
title Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE(-/-) Mice
title_full Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE(-/-) Mice
title_fullStr Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE(-/-) Mice
title_full_unstemmed Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE(-/-) Mice
title_short Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE(-/-) Mice
title_sort cathepsin k deficiency prevents the aggravated vascular remodeling response to flow cessation in apoe(-/-) mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026377/
https://www.ncbi.nlm.nih.gov/pubmed/27636705
http://dx.doi.org/10.1371/journal.pone.0162595
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