Publication

Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress

Moonen, J-R. A. J., Lee, E. S., Schmidt, M., Maleszewska, M., Koerts, J. A., Brouwer, L. A., Van Kooten, T. G., van Luyn, M. J. A., Zeebregts, C. J., Krenning, G. & Harmsen, M. C., 1-Dec-2015, In : Cardiovascular Research. 108, 3, p. 377-386 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Moonen, J-R. A. J., Lee, E. S., Schmidt, M., Maleszewska, M., Koerts, J. A., Brouwer, L. A., ... Harmsen, M. C. (2015). Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress. Cardiovascular Research, 108(3), 377-386. https://doi.org/10.1093/cvr/cvv175

Author

Moonen, Jan-Renier A. J. ; Lee, Ee Soo ; Schmidt, Marc ; Maleszewska, Monika ; Koerts, Jasper A. ; Brouwer, Linda A. ; Van Kooten, Theo G. ; van Luyn, Marja J. A. ; Zeebregts, Clark J. ; Krenning, Guido ; Harmsen, Martin C. / Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress. In: Cardiovascular Research. 2015 ; Vol. 108, No. 3. pp. 377-386.

Harvard

Moonen, J-RAJ, Lee, ES, Schmidt, M, Maleszewska, M, Koerts, JA, Brouwer, LA, Van Kooten, TG, van Luyn, MJA, Zeebregts, CJ, Krenning, G & Harmsen, MC 2015, 'Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress', Cardiovascular Research, vol. 108, no. 3, pp. 377-386. https://doi.org/10.1093/cvr/cvv175

Standard

Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress. / Moonen, Jan-Renier A. J.; Lee, Ee Soo; Schmidt, Marc; Maleszewska, Monika; Koerts, Jasper A.; Brouwer, Linda A.; Van Kooten, Theo G.; van Luyn, Marja J. A.; Zeebregts, Clark J.; Krenning, Guido; Harmsen, Martin C.

In: Cardiovascular Research, Vol. 108, No. 3, 01.12.2015, p. 377-386.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Moonen J-RAJ, Lee ES, Schmidt M, Maleszewska M, Koerts JA, Brouwer LA et al. Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress. Cardiovascular Research. 2015 Dec 1;108(3):377-386. https://doi.org/10.1093/cvr/cvv175


BibTeX

@article{b8eb5365cde44e8c82fd148cab375c68,
title = "Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress",
abstract = "Neointimal hyperplasia is a common feature of fibro-proliferative vascular disease and characterizes initial stages of atherosclerosis. Neointimal lesions mainly comprise smooth muscle-like cells. The presence of these lesions is related to local differences in shear stress. Neointimal cells may arise through migration and proliferation of smooth muscle cells from the media. However, a role for the endothelium as a source of smooth muscle-like cells has largely been disregarded. Here, we investigated the role of endothelial-to-mesenchymal transition (EndMT) in neointimal hyperplasia and atherogenesis, and studied its modulation by shear stress.In human atherosclerotic plaques and porcine aortic tissues, myo-endothelial cells were identified, suggestive for EndMT. Flow disturbance by thoracic-aortic constriction in mice similarly showed the presence of myo-endothelial cells specifically in regions exposed to disturbed flow. While uniform laminar shear stress (LSS) was found to inhibit EndMT, endothelial cells exposed to disturbed flow underwent EndMT, in vitro and in vivo, and showed atherogenic differentiation. Gain- and loss-of-function studies using a constitutive active mutant of MEK5 and short hairpins targeting ERK5 established a pivotal role for ERK5 signalling in the inhibition of EndMT.Together, these data suggest that EndMT contributes to neointimal hyperplasia and induces atherogenic differentiation of endothelial cells. Importantly, we uncovered that EndMT is modulated by shear stress in an ERK5-dependent manner. These findings provide new insights in the role of adverse endothelial plasticity in vascular disease and identify a novel atheroprotective mechanism of uniform LSS, namely inhibition of EndMT.",
keywords = "Fibrosis, Neointimal hyperplasia, Endothelial-to-mesenchymal transition, Shear stress, ERK5, SMOOTH-MUSCLE-CELL, PULMONARY-HYPERTENSION, CADHERIN EXPRESSION, ARTERIAL INJURY, GENE-EXPRESSION, IN-VIVO, ATHEROSCLEROSIS, FLOW, MYOCARDIN, GROWTH",
author = "Moonen, {Jan-Renier A. J.} and Lee, {Ee Soo} and Marc Schmidt and Monika Maleszewska and Koerts, {Jasper A.} and Brouwer, {Linda A.} and {Van Kooten}, {Theo G.} and {van Luyn}, {Marja J. A.} and Zeebregts, {Clark J.} and Guido Krenning and Harmsen, {Martin C.}",
year = "2015",
month = "12",
day = "1",
doi = "10.1093/cvr/cvv175",
language = "English",
volume = "108",
pages = "377--386",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "3",

}

RIS

TY - JOUR

T1 - Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress

AU - Moonen, Jan-Renier A. J.

AU - Lee, Ee Soo

AU - Schmidt, Marc

AU - Maleszewska, Monika

AU - Koerts, Jasper A.

AU - Brouwer, Linda A.

AU - Van Kooten, Theo G.

AU - van Luyn, Marja J. A.

AU - Zeebregts, Clark J.

AU - Krenning, Guido

AU - Harmsen, Martin C.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Neointimal hyperplasia is a common feature of fibro-proliferative vascular disease and characterizes initial stages of atherosclerosis. Neointimal lesions mainly comprise smooth muscle-like cells. The presence of these lesions is related to local differences in shear stress. Neointimal cells may arise through migration and proliferation of smooth muscle cells from the media. However, a role for the endothelium as a source of smooth muscle-like cells has largely been disregarded. Here, we investigated the role of endothelial-to-mesenchymal transition (EndMT) in neointimal hyperplasia and atherogenesis, and studied its modulation by shear stress.In human atherosclerotic plaques and porcine aortic tissues, myo-endothelial cells were identified, suggestive for EndMT. Flow disturbance by thoracic-aortic constriction in mice similarly showed the presence of myo-endothelial cells specifically in regions exposed to disturbed flow. While uniform laminar shear stress (LSS) was found to inhibit EndMT, endothelial cells exposed to disturbed flow underwent EndMT, in vitro and in vivo, and showed atherogenic differentiation. Gain- and loss-of-function studies using a constitutive active mutant of MEK5 and short hairpins targeting ERK5 established a pivotal role for ERK5 signalling in the inhibition of EndMT.Together, these data suggest that EndMT contributes to neointimal hyperplasia and induces atherogenic differentiation of endothelial cells. Importantly, we uncovered that EndMT is modulated by shear stress in an ERK5-dependent manner. These findings provide new insights in the role of adverse endothelial plasticity in vascular disease and identify a novel atheroprotective mechanism of uniform LSS, namely inhibition of EndMT.

AB - Neointimal hyperplasia is a common feature of fibro-proliferative vascular disease and characterizes initial stages of atherosclerosis. Neointimal lesions mainly comprise smooth muscle-like cells. The presence of these lesions is related to local differences in shear stress. Neointimal cells may arise through migration and proliferation of smooth muscle cells from the media. However, a role for the endothelium as a source of smooth muscle-like cells has largely been disregarded. Here, we investigated the role of endothelial-to-mesenchymal transition (EndMT) in neointimal hyperplasia and atherogenesis, and studied its modulation by shear stress.In human atherosclerotic plaques and porcine aortic tissues, myo-endothelial cells were identified, suggestive for EndMT. Flow disturbance by thoracic-aortic constriction in mice similarly showed the presence of myo-endothelial cells specifically in regions exposed to disturbed flow. While uniform laminar shear stress (LSS) was found to inhibit EndMT, endothelial cells exposed to disturbed flow underwent EndMT, in vitro and in vivo, and showed atherogenic differentiation. Gain- and loss-of-function studies using a constitutive active mutant of MEK5 and short hairpins targeting ERK5 established a pivotal role for ERK5 signalling in the inhibition of EndMT.Together, these data suggest that EndMT contributes to neointimal hyperplasia and induces atherogenic differentiation of endothelial cells. Importantly, we uncovered that EndMT is modulated by shear stress in an ERK5-dependent manner. These findings provide new insights in the role of adverse endothelial plasticity in vascular disease and identify a novel atheroprotective mechanism of uniform LSS, namely inhibition of EndMT.

KW - Fibrosis

KW - Neointimal hyperplasia

KW - Endothelial-to-mesenchymal transition

KW - Shear stress

KW - ERK5

KW - SMOOTH-MUSCLE-CELL

KW - PULMONARY-HYPERTENSION

KW - CADHERIN EXPRESSION

KW - ARTERIAL INJURY

KW - GENE-EXPRESSION

KW - IN-VIVO

KW - ATHEROSCLEROSIS

KW - FLOW

KW - MYOCARDIN

KW - GROWTH

U2 - 10.1093/cvr/cvv175

DO - 10.1093/cvr/cvv175

M3 - Article

VL - 108

SP - 377

EP - 386

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 3

ER -

ID: 29115453