GATA4 ELISA Kit

Cardiac regeneration with adult stem-cell (ASC) therapy is a promising field to address advanced cardiovascular diseases. In addition, extracellular vesicles (EVs) from ASCs have been implicated in acting as paracrine factors to improve cardiac functions in ASC therapy. In our work, we isolated human cardiac mesenchymal stromal cells (h-CMSCs) by means of three-dimensional organ culture (3D culture) during ex vivo expansion of cardiac tissue, to compare the functional efficacy with human bone-marrow derived mesenchymal stem cells (h-BM-MSCs), one of the actively studied ASCs. We characterized the h-CMSCs as CD90(low), c-kit(negative), CD105(positive) phenotype and these cells express NANOG, SOX2, and GATA4. To identify the more effective type of EVs for angiogenesis among the different sources of ASCs, we isolated EVs which were derived from CMSCs with either nomioxic or hypoxic condition and BM-MSCs. Our in vitro tube-formation results demonstrated that the angiogenic effects of EVs from hypoxia-treated CMSCs (CMSC-Hpx EVs) were greater than the well-known effects of EVs from BM-MSCs (BM-MSC EVs), and these were even comparable to human vascular endothelial growth factor (hVEGF), a potent angiogenic factor. Therefore, we present here that CD90(low)c-kit(negative)CD105(positive) CMSCs under hypoxic conditions secrete functionally superior EVs for in vitro angiogenesis. Our findings will allow more insights understanding myocardial repair.

Endothelial dysfunction is one of the most common complications associated with diabetes and may lead to atherosclerosis. Conflicting reports indicate that NADPH oxidase 4 (NOX4) induces hydrogen peroxide production and cytotoxicity, but also has a protective effect on endothelial dysfunction. The present study aimed to identify the transcription factor responsible for NOX4 expression using a transcription factor activation profiling plate array and chromatin immunoprecipitation. Data from these analyses indicated that GATA-binding protein 4 (GATA4) was able to mediate NOX4 transcription and is downregulated in human umbilical vein endothelial cells (HUVECs) that were exposed to hyperglycemic conditions as well as in the endothelial cells of a mouse diabetes model. Overexpression of GATA4 was demonstrated to lead to increased expression of NOX4 mRNA and protein. Furthermore, GATA4 overexpression resulted in increased nitric oxide (NO) production through the upregulation of endothelial NO synthase phosphorylation. Treatment with simvastatin, a drug known to preserve endothelial function through an unknown mechanism, improved endothelial cell function by upregulating GATA4 expression in HUVECs exposed to hyperglycemia. Results from these experiments demonstrated that GATA4 may inhibit diabetes-induced endothelial dysfunction by acting as a transcription factor for NOX4 expression and increasing NO production. Thus, the present study revealed a novel molecular mechanism underlying endothelial dysfunction in diabetes and identified GATA4 as a potential therapeutic target.