Upregulation of embryonic transcription factors in right ventricular hypertrophy

Increased ventricular expression of genes encoding for various structural and contractile proteins has been reported in cardiac hypertrophy. Mechanisms leading to this altered gene expression are only partly understood. Recently, various transcription factors (TF), among them GATA-4, Nkx-2.5/Csx, MEF-2 and the HAND family (eHAND and dHAND), and their role in embryonic cardiac development have been described. These transcription factors are known to have binding sites to promotor regions of many genes known to be regulated in hypertrophy of adult ventricular myocardium. We investigated the temporal and spatial expression pattern of these transcription factors in a rat model of acute pressure-overload of the right ventricle, induced by banding (coarctation) of the pulmonary artery. Expression of GATA-4, Nkx-2.5/Csx, MEF-2 and dHAND protein was found to increase in the right ventricle after the banding procedure as determined by immunohistochemistry and western blotting. A marker of the onset of cardiac hypertrophy was expression of ANP protein. We conclude that TF known to regulate embryonic heart development are involved in the adaptational response of adult ventricular myocardium to pressure overload.