Key result
Endothelium-specific RTEF-1 overexpression in mice induced significant cardiac hypertrophy after transverse aortic constriction by upregulating VEGF-B, which stimulates hypertrophic genes in cardiomyocytes.
RTEF-1-driven increase of VEGF-B plays an important role in communication between the endothelium and myocardium, promoting cardiac hypertrophy.
May implicate endothelial RTEF-1/VEGF-B signaling in pressure-overload hypertrophy; hypothesis-generating in mice and leaves open human relevance.
AIMS: Related transcription enhancer factor-1 (RTEF-1) has previously been demonstrated to play an important role in both endothelial cells and cardiomyocytes. However, the function of RTEF-1 in the communication between these two adjacent cell types has not been elucidated. METHODS AND RESULTS: We have found that endothelium-specific RTEF-1 transgenic mice (VE-Cad/RTEF-1) developed significant cardiac hypertrophy after transverse aortic constriction surgery, as evidenced by an increased ratio of heart weight to tibia length, enlarged cardiomyocyte size, thickened left ventricular wall and elevated expression of hypertrophic gene markers, with up-regulation of vascular endothelial growth factor B (VEGF-B). Additionally, VEGF-B was increased in endothelial cells from VE-Cad/RTEF-1 mice, as well as in endothelial cells with forced RTEF-1 expression (HMEC-1/RTEF-1), and coincidentally decreased when RTEF-1 was deficient in HMEC-1. Using chromatin immunoprecipitation and luciferase assays, we found that RTEF-1 increased VEGF-B promoter activity through a direct interaction. Hypertrophy-associated genes and protein synthesis were up-regulated in cardiomyocytes that were incubated with conditioned medium from HMEC-1/RTEF-1 and the endothelial cells of VE-Cad/RTEF-1 mice. This effect could be abrogated by treating the myocytes with VEGF-B small interfering RNA and extracellular signal-regulated kinase 1/2 inhibitor. CONCLUSION: Our data demonstrated that increased RTEF-1 in endothelial cells upregulates VEGF-B, which is able to stimulate hypertrophic genes in cardiomyocytes. These results suggest that the RTEF-1-driven increase of VEGF-B plays an important role in communication between the endothelium and myocardium.
No takes yet. Share an insight, caveat, or question.
Xu et al. (2010) studied Pressure overload cardiac hypertrophy. Endothelium-specific RTEF-1 overexpression was evaluated on Cardiac hypertrophy (heart weight to tibia length ratio, cardiomyocyte size, left ventricular wall thickness). Endothelium-specific RTEF-1 overexpression in mice induced significant cardiac hypertrophy after transverse aortic constriction by upregulating VEGF-B, which stimulates hypertrophic genes in cardiomyocytes.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: