%0 Journal Article
%T Modeling Cardiac Congenital Diseases: From Mathematic Tools to Human Induced Pluripotent Stem Cells
%A Laura Iop
%J Conference Papers in Science
%D 2014
%R 10.1155/2014/369246
%X Cardiac congenital diseases are rare inherited disorders characterized by anatomical malformations and/or by electrophysiological abnormalities, both affecting the whole heart function. In order to clarify the underlying pathophysiological mechanisms, experimental modeling has been proposed through in silico, in vitro, and/or in vivo simulations. Bioinformatics, transgenesis, heterologous expression systems, mammalian models, and, recently, pluripotent stem cells have been advanced to effectively recapitulate several human congenital diseases (such as Brugada syndrome, CPVT, LQTs, and ARVC) and, potentially, provide new insights into their pathomechanisms for novel therapeutic perspectives. 1. Introduction Cardiac congenital diseases are malformations of the heart, with lethal consequences in the fetal life or able to compromise the cardiovascular function often soon after birth. From simpler forms, as the atrial septal defects, to more complex abnormalities, as the complete atrioventricular canal and the Tetralogy of Fallot, such class of structural heart diseases has incidence per 1000 live births varying from an average 6.9 in Europe to 9.3 in Asia or 8 in the United States. The more severe symptoms can manifest in the first year of life: frequently, they are recognized only after infant death or when promptly diagnosed, require urgent surgical correction in approximately 25% cases. They might also be asymptomatic until the adult age in the so-called GUCH population (grown-up congenital heart) [1]. In other cases, congenital cardiac diseases are not related to morpho-anatomical defects of the heart but caused by mutations in important proteins related to its global function. In macroscopically normal hearts, ion channels, transporters, and other accessory proteins can be interested by molecular anomalies affecting their cardinal properties, thus resulting in a deregulation of the normal electromechanical coupling. Encoded by almost 350 genes, the large family of ion channels comprises proteins with a unique domain or multiple subunits, arranged in different topologies at the cell membrane. Owing to precise selective and gating features, they allow the passive flow of specific ions through their pores across the membrane interface and differ from ion pumps or sym/antiporters since they do not require energy to regulate the electrochemical movement. Many accessory proteins tune the biophysical activities of these molecular switches either as their subdomains or as specialized chaperone or anchoring units [2]. In the cardiomyocyte electromechanical
%U http://www.hindawi.com/journals/cpis/2014/369246/