Caracterização proteômica e fosfoproteômica da cardiomiopatia dilatada induzida pela deleção gênica do receptor MrgD em camundongos

Abstract

The renin angiotensin system (RAS) plays an essential role in the cardiovascular homeostasis. Several enzymes, active peptides and receptors are regulating RAS during physiological and pathological conditions. Recently, a study showed that deletion of a RAS component (MrgD gene) led to a significant left ventricular remodeling, developing severe dilated cardiomyopathy (DCM) in mice. DCM is a disease of the cardiac muscle characterized by enlargement and dilation of one or both of the ventricles along with impaired contractility. Moreover, DCM is the most common reason for heart transplantation worldwide. Therefore, we aimed to perform a proteomic and phosphoproteomic characterization of the cardiac tissues and cardiac cells derived from mice without MRGD gene for a better understanding of the role of this receptor in DCM. Thus, the left ventricle, the ventricular cardiomyocytes and the extracellular matrix from MrgD-knockout (mrgd-ko) and C57Bl6 (wt) adult mice were submitted to proteomics analysis. Functional proteomics analysis showed that MrgD deletion triggers significant changes in pathways related to ionic homeostasis, muscle contraction, adrenergic signaling, sarcomere organization and focal adhesion.