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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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Volume 384, Issue 3


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


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.

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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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