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European Heart Journal Advance Access published online on June 27, 2009
European Heart Journal, doi:10.1093/eurheartj/ehp267
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org

Cardiomyopathy is associated with structural remodelling of heart valve extracellular matrix

Katja Schenke-Layland1,2,*, Ulrich A. Stock2,3, Ali Nsair1, Jiansong Xie4, Ekaterini Angelis1, Carissa G. Fonseca5, Robert Larbig1, Aman Mahajan6, Kalyanam Shivkumar1, Michael C. Fishbein7 and William R. MacLellan

1 Department of Medicine/Cardiology, Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
2 Department of Cardiothoracic and Vascular Surgery, Friedrich-Schiller-University, Jena, Germany
3 Department of Thoracic, Cardiac and Vascular Surgery, University of Tübingen, Tübingen, Germany
4 Department of Pharmacology and Pharmaceutical Sciences, USC, Los Angeles, CA, USA
5 Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
6 Department of Anaesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
7 Department of Pathology/Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

Received 23 August 2008; revised 26 May 2009; accepted 10 June 2009 * Corresponding author. Tel: +1 310 206 6477, Fax: +1 310 206 5777, Email: kschenkelayland{at}mednet.ucla.edu

Aims: To increase the supply, many countries harvest allograft valves from explanted hearts of transplant recipients with ischaemic (ICM) or dilated cardiomyopathy (DCM). This study determines the structural integrity of valves from cardiomyopathic hearts.

Methods and results: Extracellular matrix (ECM) was examined in human valves obtained from normal, ICM, and DCM hearts. To confirm if ECM changes were directly related to the cardiomyopathy, we developed a porcine model of chronic ICM. Histology and immunohistostaining, as well as non-invasive multiphoton and second harmonic generation (SHG) imaging revealed marked disruption of ECM structures in human valves from ICM and DCM hearts. The ECM was unaffected in valves from normal and acute ICM pigs, whereas chronic ICM specimens showed ECM alterations similar to those seen in ICM and DCM patients. Proteins and proteinases implicated in ECM remodelling, including Tenascin C, TGFβ1, Cathepsin B, MMP2, were upregulated in human ICM and DCM, and porcine chronic ICM specimens.

Conclusion: Valves from cardiomyopathic hearts showed significant ECM deterioration with a disrupted collagen and elastic fibre network. It will be important to determine the impact of this ECM damage on valve durability and calcification in vivo if allografts are to be used from these donors.

Key Words: Heart valves • Cardiomyopathy • Extracellular matrix • Collagen • Remodelling


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