Chapters authored
Idiopathic Dilated Cardiomyopathy: Molecular Basis and Distilling Complexity to Advance
Cardiomyopathies are heterogeneous diseases of the myocardium associated with abnormal findings of chamber size, wall thickness, and/or functional contractility. In particular, dilated cardiomyopathy (DCM) is mainly characterized by ventricular chamber enlargement with systolic dysfunction and normal left ventricular (LV) wall thickness. Although DCM is thought to be induced mainly by genetic or environmental factors, in the majority of cases, the cause is unknown. With an estimated prevalence of 1:2500 and an incidence of 1:18,000 per year in adults, DCM is the most frequent indication for heart transplantation, which represents an enormous cost burden on healthcare systems. These figures warrant greater accuracy in patient diagnosis and prognosis and further insight into the underlying basis of DCM. Here, we discuss past and recent findings on the molecular mechanisms involved in DCM. Dilated cardiomyopathy has been linked to the overactivation of extracellular signal-regulated kinase (ERK1/2), which in turn is related to activation of low-density lipoprotein receptor–related protein-1 (LRP-1). Moreover, a redistribution of LRP-1 into cholesterol-enriched plasma membrane domains (lipid rafts) and alterations in cardiac DNA methylation have been reported in failing hearts. In conclusion, more comprehensive analyses of myocardial lipid rafts and epigenetic mechanisms may advance our understanding of DCM causes and progression. In turn, this understanding may promote the development of innovative treatments.
Part of the book: Cardiomyopathies