Role of cardiac TBX20 in dilated cardiomyopathy

Abstract

Dilated cardiomyopathy (DCM) is an important cause of heart failure and sudden cardiac death worldwide. Transcription factor TBX20 has been shown to play a crucial role in cardiac development and maintenance of adult mouse heart. Recent studies suggest that TBX20 may have a role in pathophysiology of DCM. In the present study, we examined TBX20 expression in idiopathic DCM patients and in an animal model of cardiomyopathy, and studied its correlation with echocardiographic indices of LV function. Endomyocardial biopsies (EMBs) from intraventricular septal from the right ventricle region were obtained from idiopathic DCM patients (IDCM, n = 30) and from patients with ventricular septal defect (VSD, n = 14) with normal LVEF who served as controls. An animal model of DCM was developed by right renal artery ligation in Wistar rats. Cardiac TBX20 mRNA levels were measured by real-time PCR in IDCM, controls, and in rats. The role of DNA promoter methylation and copy number variation (CNVs) in regulating TBX20 gene expression was also investigated. Cardiac TBX20 mRNA levels were significantly increased (8.9 fold, p < 0.001) in IDCM patients and in RAL rats as compared to the control group. Cardiac TBX20 expression showed a negative correlation with LVEF (r = -0.71, p < 0.001) and a positive correlation with left ventricular end-systolic volume (r = 0.39, p = 0.038). No significant difference in TBX20 CNVs and promoter methylation was observed between IDCM patients and control group. Our results suggest a potential role of TBX20 in pathophysiology of DCM.

A context-specific cardiac β-catenin and GATA4 interaction influences TCF7L2 occupancy and remodels chromatin driving disease progression in the adult heart

“…A previous study associated TCF7L2 activation with the ubiquitous Wnt target c-Myc in the heart ( 7 ). Using integrative, unbiased genome-wide analyses, we identified and validated novel TCF7L2 cardiac-specific target genes involved in tissue remodelling- such as Hand2, Tbx20, Rock2 and Dstn ( 40 , 42 , 43 , 57 ). β-catenin stabilization induced TCF7L2 recruitment to distal regions of these novel targets in the heart, but not in liver; whereas recruitment of TCF7L2 to proximal regions of ubiquitously described Wnt targets Axin2 and Lef1 was induced in both tissues.…”

Repair Injured Heart by Regulating Cardiac Regenerative Signals

“…Increased TBX20 gene expression was observed in endomyocardial biopsies from idiopathic dilated cardiomyopathy patients and animal models of cardiomyopathy that are associated with compromised heart performance [ 108 ], and upregulation of this gene is considered an adaptive response of a stressed heart. In the loss-of-function experiments, chamber dilation was observed in TBX20 knockout mouse hearts, and cardiomyocyte-specific ablation of this transcription factor resulted in animal lethality within 15 days [ 75 ].…”

Maternal Folic Acid Intake and Methylation Status of Genes Associated with Ventricular Septal Defects in Children: Case–Control Study

“…Mutations in the coding region of TBX20 have been associated with sporadic and familial cases of coronary heart disease, including atrial septal defects (ASD), tetralogy of Fallot, and dilated cardiomyopathy in adults [ 8 ]. Furthermore, differences in the methylation patterns between subjects with dilated heart disease and VSD have been observed in the promoter region of TBX20 [ 13 ].…”