T-cadherin is present on endothelial microparticles and is elevated in plasma in early atherosclerosis

Maria Philippova, Yves Suter, Stefan Toggweiler, Andreas W. Schoenenberger, Manjunath B. Joshi, Emmanouil Kyriakakis, Paul Erne, Thérèse J. Resink

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Aims The presence of endothelial cell (EC)-derived surface molecules in the circulation is among hallmarks of endothelial activation and damage in vivo. Previous investigations suggest that upregulation of T-cadherin (T-cad) on the surface of ECs may be a characteristic marker of EC activation and stress. We investigated whether T-cad might also be shed from ECs and in amounts reflecting the extent of activation or damage. Methods and resultsImmunoblotting showed the presence of T-cad protein in the culture medium from normal proliferating ECs and higher levels in the medium from stressed/apoptotic ECs. Release of T-cad into the circulation occurs in vivo and in association with endothelial dysfunction. Sandwich ELISA revealed negligible T-cad protein in the plasma of healthy volunteers (0.90 ± 0.90 ng/mL, n 30), and increased levels in the plasma from patients with non-significant atherosclerosis (9.23 ± 2.61 ng/mL, n 63) and patients with chronic coronary artery disease (6.93 ± 1.31 ng/mL, n 162). In both patient groups there was a significant (P 0.043) dependency of T-cad and degree of endothelial dysfunction as measured by reactive hyperaemia peripheral tonometry. Flow cytometry analysis showed that the major fraction of T-cad was released into the EC culture medium and the plasma as a surface component of EC-derived annexin V- and CD144/CD31-positive microparticles (MPs). Gain-of-function and loss-of-function studies demonstrate that MP-bound T-cad induced Akt phosphorylation and activated angiogenic behaviour in target ECs via homophilic-based interactions.Conclusion Our findings reveal a novel mechanism of T-cad-dependent signalling in the vascular endothelium. We identify T-cad as an endothelial MP antigen in vivo and demonstrate that its level in plasma is increased in early atherosclerosis and correlates with endothelial dysfunction.

Original languageEnglish
Pages (from-to)760-771
Number of pages12
JournalEuropean Heart Journal
Volume32
Issue number6
DOIs
Publication statusPublished - 03-2011

Fingerprint

Atherosclerosis
Endothelial Cells
Culture Media
Annexin A5
Hyperemia
Manometry
Vascular Endothelium
Coronary Artery Disease
Healthy Volunteers
Flow Cytometry
Up-Regulation
Cell Culture Techniques
Enzyme-Linked Immunosorbent Assay
Phosphorylation
Antigens
H-cadherin

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Philippova, M., Suter, Y., Toggweiler, S., Schoenenberger, A. W., Joshi, M. B., Kyriakakis, E., ... Resink, T. J. (2011). T-cadherin is present on endothelial microparticles and is elevated in plasma in early atherosclerosis. European Heart Journal, 32(6), 760-771. https://doi.org/10.1093/eurheartj/ehq206
Philippova, Maria ; Suter, Yves ; Toggweiler, Stefan ; Schoenenberger, Andreas W. ; Joshi, Manjunath B. ; Kyriakakis, Emmanouil ; Erne, Paul ; Resink, Thérèse J. / T-cadherin is present on endothelial microparticles and is elevated in plasma in early atherosclerosis. In: European Heart Journal. 2011 ; Vol. 32, No. 6. pp. 760-771.
@article{d5f8e4e935d04bbda7682ce27aa2ccf5,
title = "T-cadherin is present on endothelial microparticles and is elevated in plasma in early atherosclerosis",
abstract = "Aims The presence of endothelial cell (EC)-derived surface molecules in the circulation is among hallmarks of endothelial activation and damage in vivo. Previous investigations suggest that upregulation of T-cadherin (T-cad) on the surface of ECs may be a characteristic marker of EC activation and stress. We investigated whether T-cad might also be shed from ECs and in amounts reflecting the extent of activation or damage. Methods and resultsImmunoblotting showed the presence of T-cad protein in the culture medium from normal proliferating ECs and higher levels in the medium from stressed/apoptotic ECs. Release of T-cad into the circulation occurs in vivo and in association with endothelial dysfunction. Sandwich ELISA revealed negligible T-cad protein in the plasma of healthy volunteers (0.90 ± 0.90 ng/mL, n 30), and increased levels in the plasma from patients with non-significant atherosclerosis (9.23 ± 2.61 ng/mL, n 63) and patients with chronic coronary artery disease (6.93 ± 1.31 ng/mL, n 162). In both patient groups there was a significant (P 0.043) dependency of T-cad and degree of endothelial dysfunction as measured by reactive hyperaemia peripheral tonometry. Flow cytometry analysis showed that the major fraction of T-cad was released into the EC culture medium and the plasma as a surface component of EC-derived annexin V- and CD144/CD31-positive microparticles (MPs). Gain-of-function and loss-of-function studies demonstrate that MP-bound T-cad induced Akt phosphorylation and activated angiogenic behaviour in target ECs via homophilic-based interactions.Conclusion Our findings reveal a novel mechanism of T-cad-dependent signalling in the vascular endothelium. We identify T-cad as an endothelial MP antigen in vivo and demonstrate that its level in plasma is increased in early atherosclerosis and correlates with endothelial dysfunction.",
author = "Maria Philippova and Yves Suter and Stefan Toggweiler and Schoenenberger, {Andreas W.} and Joshi, {Manjunath B.} and Emmanouil Kyriakakis and Paul Erne and Resink, {Th{\'e}r{\`e}se J.}",
year = "2011",
month = "3",
doi = "10.1093/eurheartj/ehq206",
language = "English",
volume = "32",
pages = "760--771",
journal = "European Heart Journal",
issn = "0195-668X",
publisher = "Oxford University Press",
number = "6",

}

Philippova, M, Suter, Y, Toggweiler, S, Schoenenberger, AW, Joshi, MB, Kyriakakis, E, Erne, P & Resink, TJ 2011, 'T-cadherin is present on endothelial microparticles and is elevated in plasma in early atherosclerosis', European Heart Journal, vol. 32, no. 6, pp. 760-771. https://doi.org/10.1093/eurheartj/ehq206

T-cadherin is present on endothelial microparticles and is elevated in plasma in early atherosclerosis. / Philippova, Maria; Suter, Yves; Toggweiler, Stefan; Schoenenberger, Andreas W.; Joshi, Manjunath B.; Kyriakakis, Emmanouil; Erne, Paul; Resink, Thérèse J.

In: European Heart Journal, Vol. 32, No. 6, 03.2011, p. 760-771.

Research output: Contribution to journalArticle

TY - JOUR

T1 - T-cadherin is present on endothelial microparticles and is elevated in plasma in early atherosclerosis

AU - Philippova, Maria

AU - Suter, Yves

AU - Toggweiler, Stefan

AU - Schoenenberger, Andreas W.

AU - Joshi, Manjunath B.

AU - Kyriakakis, Emmanouil

AU - Erne, Paul

AU - Resink, Thérèse J.

PY - 2011/3

Y1 - 2011/3

N2 - Aims The presence of endothelial cell (EC)-derived surface molecules in the circulation is among hallmarks of endothelial activation and damage in vivo. Previous investigations suggest that upregulation of T-cadherin (T-cad) on the surface of ECs may be a characteristic marker of EC activation and stress. We investigated whether T-cad might also be shed from ECs and in amounts reflecting the extent of activation or damage. Methods and resultsImmunoblotting showed the presence of T-cad protein in the culture medium from normal proliferating ECs and higher levels in the medium from stressed/apoptotic ECs. Release of T-cad into the circulation occurs in vivo and in association with endothelial dysfunction. Sandwich ELISA revealed negligible T-cad protein in the plasma of healthy volunteers (0.90 ± 0.90 ng/mL, n 30), and increased levels in the plasma from patients with non-significant atherosclerosis (9.23 ± 2.61 ng/mL, n 63) and patients with chronic coronary artery disease (6.93 ± 1.31 ng/mL, n 162). In both patient groups there was a significant (P 0.043) dependency of T-cad and degree of endothelial dysfunction as measured by reactive hyperaemia peripheral tonometry. Flow cytometry analysis showed that the major fraction of T-cad was released into the EC culture medium and the plasma as a surface component of EC-derived annexin V- and CD144/CD31-positive microparticles (MPs). Gain-of-function and loss-of-function studies demonstrate that MP-bound T-cad induced Akt phosphorylation and activated angiogenic behaviour in target ECs via homophilic-based interactions.Conclusion Our findings reveal a novel mechanism of T-cad-dependent signalling in the vascular endothelium. We identify T-cad as an endothelial MP antigen in vivo and demonstrate that its level in plasma is increased in early atherosclerosis and correlates with endothelial dysfunction.

AB - Aims The presence of endothelial cell (EC)-derived surface molecules in the circulation is among hallmarks of endothelial activation and damage in vivo. Previous investigations suggest that upregulation of T-cadherin (T-cad) on the surface of ECs may be a characteristic marker of EC activation and stress. We investigated whether T-cad might also be shed from ECs and in amounts reflecting the extent of activation or damage. Methods and resultsImmunoblotting showed the presence of T-cad protein in the culture medium from normal proliferating ECs and higher levels in the medium from stressed/apoptotic ECs. Release of T-cad into the circulation occurs in vivo and in association with endothelial dysfunction. Sandwich ELISA revealed negligible T-cad protein in the plasma of healthy volunteers (0.90 ± 0.90 ng/mL, n 30), and increased levels in the plasma from patients with non-significant atherosclerosis (9.23 ± 2.61 ng/mL, n 63) and patients with chronic coronary artery disease (6.93 ± 1.31 ng/mL, n 162). In both patient groups there was a significant (P 0.043) dependency of T-cad and degree of endothelial dysfunction as measured by reactive hyperaemia peripheral tonometry. Flow cytometry analysis showed that the major fraction of T-cad was released into the EC culture medium and the plasma as a surface component of EC-derived annexin V- and CD144/CD31-positive microparticles (MPs). Gain-of-function and loss-of-function studies demonstrate that MP-bound T-cad induced Akt phosphorylation and activated angiogenic behaviour in target ECs via homophilic-based interactions.Conclusion Our findings reveal a novel mechanism of T-cad-dependent signalling in the vascular endothelium. We identify T-cad as an endothelial MP antigen in vivo and demonstrate that its level in plasma is increased in early atherosclerosis and correlates with endothelial dysfunction.

UR - http://www.scopus.com/inward/record.url?scp=79952856179&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952856179&partnerID=8YFLogxK

U2 - 10.1093/eurheartj/ehq206

DO - 10.1093/eurheartj/ehq206

M3 - Article

C2 - 20584775

AN - SCOPUS:79952856179

VL - 32

SP - 760

EP - 771

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - 6

ER -