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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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1437-4315
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Volume 384, Issue 3

Issues

Induction of Apoptosis in Vascular Cells by Plasminogen Activator Inhibitor-1 and High Molecular Weight Kininogen Correlates with Their Anti-Adhesive Properties

N. Al-Fakhri / T. Chavakis / T. Schmidt-Wöll / B. Huang / S.M. Cherian / Y.V. Bobryshev / R.S.A. Lord / N. Katz / K.T. Preissner
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.2003.048

Abstract

Plasminogen activator inhibitor-1 (PAI-1) and twochain high molecular weight kininogen (HKa) exert antiadhesive properties in vitronectindependent cell adhesion. Here, the hypothesis was tested that these anti-adhesive components promote apoptosis in vascular cells. PAI-1 or HKa induced a 2- to 3-fold increase in apoptosis of human umbilicalvein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC) adherent to vitronectin, as determined by annexin VFACS assay, similar to αvintegrin inhibitor cyclo-(Arg-Gly-Asp-D-Phe-Val)-peptide (cRGDfV). Apoptosis occurred after 12 h incubation and was attributable to caspase 3 activation that in turn induced DNA fragmentation. Induction of apoptosis strongly correlated with the antiadhesive effect of PAI-1 and HKa on these cells. In contrast, PAI-1 and HKa did not affect fibronectin-dependent adhesion or cell survival. uPA did not influence apoptosis in vitronectin- or fibronectin-adherent cells. In atherosclerotic vessel sections, congruent distribution of vitronectin, PAI-1, HK, and of components of the urokinase plasminogen activator/receptor system with apoptotic cells lining foam cell lesions was demonstrated by immunostaining. These results indicate that inhibition of vitronectindependent cell adhesion through PAI-1 and HKa correlates with apoptosis induction in vascular cells mediated through the caspase 3 pathway. Co-distribution of apoptosis with plasminogen activation system components in atherosclerosis exemplifies the significance of antiadhesive mechanisms and apoptosis for tissue remodeling, such as in neointima development.

About the article

Published Online: 2005-06-01

Published in Print: 2003-03-14


Citation Information: Biological Chemistry, Volume 384, Issue 3, Pages 423–435, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2003.048.

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