Pathophysiology and pathological remodelling associated with dilated cardiomyopathy in broiler chickens predisposed to heart pump failure

Abstract

ABSTRACT Broiler chickens selected for rapid growth are highly susceptible to dilated cardiomyopathy (DCM). In order to elucidate the pathophysiology of DCM, the present study examines the fundamental features of pathological remodelling associated with DCM in broiler chickens using light microscopy, transmission electron microscopy (TEM), and synchrotron Fourier Transform Infrared (FTIR) micro-spectroscopy. The morphological features and FTIR spectra of the left ventricular myocardium were compared among broiler chickens affected by DCM with clinical signs of heart pump failure, apparently normal fast-growing broiler chickens showing signs of subclinical DCM (high risk of heart failure), slow-growing broiler chickens (low risk of heart failure) and Leghorn chickens (resistant to heart failure, used here as physiological reference). The findings indicate that DCM and heart pump failure in fast-growing broiler chickens are a result of a complex metabolic syndrome involving multiple catabolic pathways. Our data indicate that a good deal of DCM pathophysiology in chickens selected for rapid growth is associated with conformational changes of cardiac proteins, and pathological changes indicative of accumulation of misfolded and aggregated proteins in the affected cardiomyocytes. From TEM image analysis it is evident that the affected cardiomyocytes demonstrate significant difficulty in the disposal of damaged proteins and maintenance of proteostasis, which leads to pathological remodelling of the heart and contractile dysfunction. It appears that the underlying causes of accumulation of damaged proteins are associated with dysregulated auto phagosome and proteasome systems, which, in susceptible individuals, create a milieu conducive for the development of DCM and heart failure. RESEARCH HIGHLIGHTS The light and electron microscopy image analyses revealed degenerative changes and protein aggregates in the cardiomyocytes of chickens affected by DCM. The analyses of FTIR spectra of the myocardium revealed that DCM and heart pump failure in broiler chickens are associated with conformational changes of myocardial proteins. The morphological changes in cardiomyocytes and conformational changes in myocardial proteins architecture are integral constituents of pathophysiology of DCM in fast-growing broiler chickens.