Regional mapping of myocardial hibernation phenotype in idiopathic end-stage dilated cardiomyopathy.
Myocardial hibernation (MH) is a well-known feature of human ischaemic cardiomyopathy (ICM), whereas its presence in human idiopathic dilated cardiomyopathy (DCM) is still controversial. We investigated the histological and molecular features of MH in left ventricle (LV) regions of failing DCM or ICM hearts. We examined failing hearts from DCM (n = 11; 41.9 ± 5.45 years; left ventricle-ejection fraction (LV-EF), 18 ± 3.16%) and ICM patients (n = 12; 58.08 ± 1.7 years; LVEF, 21.5 ± 6.08%) undergoing cardiac transplantation, and normal donor hearts (N, n = 8). LV inter-ventricular septum (IVS) and antero-lateral free wall (FW) were transmurally (i.e. sub-epicardial, mesocardial and sub-endocardial layers) analysed. LV glycogen content was shown to be increased in both DCM and ICM as compared with N hearts (P < 0.001), with a U-shaped transmural distribution (lower values in mesocardium). Capillary density was homogenously reduced in both DCM and ICM as compared with N (P < 0.05 versus N), with a lower decrease independent of the extent of fibrosis in sub-endocardial and sub-epicardial layers of DCM as compared with ICM. HIF1-α and nestin, recognized ischaemic molecular hallmarks, were similarly expressed in DCM-LV and ICM-LV myocardium. The proteomic profile was overlapping by ~50% in DCM and ICM groups. Morphological and molecular features of MH were detected in end-stage ICM as well as in end-stage DCM LV, despite epicardial coronary artery patency and lower fibrosis in DCM hearts. Unravelling the presence of MH in the absence of coronary stenosis may be helpful to design a novel approach in the clinical management of DCM.
Laboratory of Medical Science, Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy; Fondazione CNR-Regione Toscana "G. Monasterio", Pisa, Italy.
Vincenzo
V
Lionetti
Marco
M
Matteucci
Marco
M
Ribezzo
Dario
D
Di Silvestre
Francesca
F
Brambilla
Silvia
S
Agostini
Pierluigi
P
Mauri
Luigi
L
Padeletti
Alessandro
A
Pingitore
Luisa
L
Delsedime
Mauro
M
Rinaldi
Fabio A
FA
Recchia
Angela
A
Pucci
D000328:Adult; D017209:Apoptosis; D002196:Capillaries / Q000473:pathology; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D048429:Cell Size; D024042:Collagen Type I / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006333:Heart Failure / Q000473:pathology; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000473:pathology; D017682:Myocardial Stunning / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D010641:Phenotype; D040901:Proteomics; D014463:Ultrasonography; D014746:Vimentin / Q000378:metabolism
D024042:Collagen Type I; D018031:Connexin 43; D005353:Fibronectins; D014746:Vimentin
chronic heart failure; hibernating myocardium; idiopathic dilated cardiomyopathy; ischaemic microenvironment; nestin; pathologic features