Cardiomyopathy is associated with structural remodelling of heart valve extracellular matrix.
OBJECTIVE
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.


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, TGFbeta1, Cathepsin B, MMP2, were upregulated in human ICM and DCM, and porcine chronic ICM specimens.


CONCLUSIONS
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.
Schenke-Layland
Katja
K
Department of Medicine/Cardiology, Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. kschenkelayland@mednet.ucla.edu
Stock
Ulrich A
UA
Nsair
Ali
A
Xie
Jiansong
J
Angelis
Ekaterini
E
Fonseca
Carissa G
CG
Larbig
Robert
R
Mahajan
Aman
A
Shivkumar
Kalyanam
K
Fishbein
Michael C
MC
MacLellan
William R
WR
D000368:Aged; D000818:Animals; D009202:Cardiomyopathies / Q000201:enzymology / Q000473:pathology*; D002908:Chronic Disease; D005109:Extracellular Matrix / Q000201:enzymology / Q000473:pathology*; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D006351:Heart Valves / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D008297:Male; D036641:Microscopy, Fluorescence, Multiphoton; D008875:Middle Aged; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology; D013552:Swine
D018093:Gelatinases