Endothelial differentiation gene-1, a new downstream gene is involved in RTEF-1 induced angiogenesis in endothelial cells.

Related Transcriptional Enhancer Factor-1 (RTEF-1) has been suggested to induce angiogenesis through regulating target genes. Whether RTEF-1 has a direct role in angiogenesis and what specific genes are involved in RTEF-1 driven angiogenisis have not been elucidated. We found that over-expressing RTEF-1 in Human dermal microvascular endothelial cells-1 (HMEC-1) significantly increased endothelial cell aggregation, growth and migration while the processes were inhibited by siRNA of RTEF-1.

Endothelial cells require related transcription enhancer factor-1 for cell-cell connections through the induction of gap junction proteins.

Objective: Capillary network formation represents a specialized endothelial cell function and is a prerequisite to establish a continuous vessel lumen. Formation of endothelial cell connections that form the vascular structure is regulated, at least in part, at the transcriptional level. We report here that related transcription enhancer factor-1 (RTEF-1) plays an important role in vascular structure formation.

Panax notoginseng and its components decreased hypertension via stimulation of endothelial-dependent vessel dilatation.

Unlabelled: Ginsenoside Rb1 and Rg1 are major components of Panax notoginseng (P.N.), an herb with known clinical efficacy in hypertension and myocardial ischemia in Eastern countries.

The endothelium-dependent effect of RTEF-1 in pressure overload cardiac hypertrophy: role of VEGF-B.

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).

Hypoxia-regulated angiogenic inhibitors.

The regulation of angiogenesis by hypoxia is an essential homeostatic mechanism that depends on a precise balance between positive and negative angiogenic regulatory molecules. Proangiogenic factors are well characterized; however, several in vivo and in vitro studies indicate that there are feedback mechanisms in place to inhibit angiogenesis during hypoxia. Understanding the signaling pathways leading to the negative feedback of angiogenesis will undoubtedly provide important tools to develop novel therapeutic strategies not only to enhance the angiogenic response in coronary artery disease but also to hinder deregulated angiogenesis in tumorigenesis.

Hyperglycemia attenuates angiogenic capability of survivin in endothelial cells.

Survivin, an anti-apoptotic protein, can be induced by hypoxia and contributes to angiogenic activity in endothelial cells. To determine the potential mechanism of survivin in endothelial dysfunction caused by hyperglycemia in diabetes, we evaluated the role of survivin in hyperglycemia and its effect on endothelial homeostasis. We demonstrated that an increase of D-glucose was sufficient to down-regulate survivin expression, impacting survivin's angiogenic role in endothelial cells.

Response gene to complement 32, a novel hypoxia-regulated angiogenic inhibitor.

Background: Response gene to complement 32 (RGC-32) is induced by activation of complement and regulates cell proliferation. To determine the mechanism of RGC-32 in angiogenesis, we examined the role of RGC-32 in hypoxia-related endothelial cell function.

Methods And Results: Hypoxia/ischemia is able to stimulate both angiogenesis and apoptosis.

RGS5, a hypoxia-inducible apoptotic stimulator in endothelial cells.

Endothelial cells rapidly respond to changes in oxygen homeostasis by regulating gene expression. Regulator of G protein signaling 5 (RGS5) is a negative regulator of G protein-mediated signaling that is strongly expressed in vessels during angiogenesis; however, the role of RGS5 in hypoxia has not been fully understood. Under hypoxic conditions, we found that the expression of RGS5, but not other RGS, was induced in human umbilical vein endothelial cells (HUVEC).

Induction of regulatory T cells by physiological level estrogen.

Naturally occurring CD4+CD25+ regulatory T cells (Treg) exert an important role in mediating maternal tolerance to the fetus during pregnancy, and this effect might be regulated via maternal estrogen secretion. Although estrogen concentration in the pharmaceutical range has been shown to drive expansion of CD4+CD25+ Treg cells, little is known about how and through what mechanisms E2 within the physiological concentration range of pregnancy affects this expansion. Using in vivo and in vitro mouse models in these experiments, we observed that E2 at physiological doses not only expanded Treg cell in different tissues but also increased expression of the Foxp3 gene, a hallmark for CD4+CD25+ Treg cell function, and the IL-10 gene as well.