Regional mapping of myocardial hibernation phenotype in idiopathic end‐stage dilated cardiomyopathy

Abstract

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.

Myocardial expression analysis of osteopontin and its splice variants in patients affected by end-stage idiopathic or ischemic dilated cardiomyopathy

“…We have detected larger myocardial deposits of type I collagen, fibronectin and fibroblasts in ICM rather than DCM hearts [31], in accord with previous studies [34][35][36][37][38]. Our data are also consistent with proteomic analysis performed by us on the same LV samples [31], which show the up-regulation of pro-apoptotic and pro-fibrotic factors in ICM failing hearts with overt fibrosis (ICM). In addition, we argue that the proteolytic cleavage of OPN-a in DCM samples may be independent on thrombin, which levels are similarly increased to those of OPN-a.…”

“…Cathepsin D, an aspartyl lysosomal protease, is able to cleave OPN-a at the level of RGD domain [40], an arginine-glycine-aspartic acid domain that is also recognized by thrombin and plasmin [40], cell surface integrins expressed by fibroblasts [41] or non-RGD integrins, such as α4β1 and α9β1 [3,42,43]. In our samples, the LV cathepsin-D expression was up-regulated in ICM rather than DCM failing hearts [31]. The above mentioned proteomic findings well support the detection of higher levels of OPN-a in the presence of higher thrombin levels in our DCM failing hearts.…”

Identification of new biophysical markers for pathological ventricular remodelling in tachycardia‐induced dilated cardiomyopathy

“…Haemodynamic measurements showed decreased contractility without a significant increase in the ventricular filling pressures. Previous studies have suggested that mechanical dyssynchrony, in the absence of coronary stenosis, can cause myocardial hibernation . Therefore, we tested the presence of molecular mechanisms associated to myocardial hibernation in our in vivo model.…”

Hibernation of Myocardium in the Case of Neuroleptic Cardiomyopathy: A Statistical Analysis

“…Reports about HM in cases of cardiomyopathies, a diabetic cardiomyopathy [8] and idiopathic dilated one (DCMP) [9] indeed appeared recently. However there are no reports about HM in cases of neuroleptic cardiomyopathy (NCMP) in literature although NCMP belongs to specific (secondary) DCMP's [10] as well as ICMP, but HM is quite often observed in cases of ICMP [6].…”