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Loss of β1D-integrin function in human ischemic cardiomyopathy

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Abstract

Integrins play a pivotal role in cardiomyocyte survival and function, with integrin loss leading to myocyte apoptosis and heart failure. The aim of this study was to characterize whether regulation of integrins may contribute to cardiac remodeling in human ischemic cardiomyopathy (ICM).

Myocardial tissues of the left ventricle were obtained from patients with ICM (n = 8) undergoing cardiac transplantation and from unused donor hearts (NF, n = 8). In addition, tissue samples from patients with dilated cardiomyopathy (DCM, n = 5) were analyzed. Expression of integrins β1D and β3, the effector proteins focal adhesion kinase (FAK) and melusin, and FAK phosphorylation were examined by Western blotting, real-time-PCR and immunofluorescence analysis, respectively. β1D-integrin protein was decreased in ICM vs. NF by 36%. β1D-integrin mRNA levels and β1D-integrin shedding were unchanged. Corresponding to β1D-integrin regulation, FAK and phosphorylated FAK were decreased in ICM vs. NF by 54% and 49%, respectively. β3-integrin and melusin were not altered in ICM. As a mediator of integrin effects, AKT kinase activity was examined. In parallel to β1D-integrin and FAK, AKT activity was decreased in ICM by 44%. In contrast, none of the proteins were significantly altered in DCM compared to NF.

Integrins and integrin signaling are regulated differentially in ICM and DCM with a decrease of β1D-integrin and FAK in ICM. The loss of the β1Dintegrin-FAK-complex in ICM was paralleled by a reduced AKT activity supporting in vitro data which demonstrate the pivotal role of intact integrin function in anti-apoptotic signaling and cell survival.

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Authors and Affiliations

  1. Dept. III of Internal Medicine, University of Cologne, Josef-Stelzmann-Str. 9, 50924, Cologne, Germany

    R. Pfister, C. Acksteiner, J. Baumgarth, V. Burst & M. Flesch MD

  2. Dept. of Cardiothoracic Surgery, University of Cologne, Cologne, Germany

    H. J. Geissler

  3. University of Pennsylvania, School of Medicine, Philadelphia (PA), USA

    K. B. Margulies

  4. Temple University, Philadelphia (PA), USA

    S. Houser

  5. Dept. of Cellular and Molecular Sport Medicine, German Sport University Cologne, Cologne, Germany

    W. Bloch

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  1. R. Pfister
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  2. C. Acksteiner
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  3. J. Baumgarth
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  4. V. Burst
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  5. H. J. Geissler
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  6. K. B. Margulies
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  7. S. Houser
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  8. W. Bloch
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  9. M. Flesch MD
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Correspondence to M. Flesch MD.

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Pfister, R., Acksteiner, C., Baumgarth, J. et al. Loss of β1D-integrin function in human ischemic cardiomyopathy. Basic Res Cardiol 102, 257–264 (2007). https://doi.org/10.1007/s00395-006-0640-1

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  • DOI: https://doi.org/10.1007/s00395-006-0640-1

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