NR4A3 induces endothelial dysfunction through up-regulation of endothelial 1 expression in adipose tissue-derived stromal cells

Hypertension is one of the most prevalent diseases worldwide. Increased synthesis of the vasoconstrictor peptide endothelin 1 (encoded by EDN1) might be responsible for high blood pressure. The present study further confirmed the abnormal EDN1 upregulation within adipose tissue-derived stromal cells (ADSCs) derived from morbidly obese subjects. The overexpression of EDN1 in ADSCs derived from non-obese subjects significantly promoted the proliferation and migration of HUVECs and tube formation by human umbilical vein endothelial cell (HUVEC). Transcription factor NR4A3 was positively correlated with EDN1, binding to EDN1 promoter region to upregulate EDN1 expression. Similarly, the overexpression of NR4A3 in ADSCs derived from non-obese subjects significantly promoted the proliferation and migration of HUVECs and tube formation by HUVECs, as well as EDN1 protein levels in ADSCs. However, the effects of NR4A3 overexpression on EDN1 protein levels in ADSCs and the proliferation and migration of HUVECs and tube formation by HUVECs were significantly reversed by EDN1 silencing in ADSCs. In conclusion, NR4A3 is abnormally upregulated in ADSCs derived from morbidly obese subjects; NR4A3 could promote HUVEC angiogenesis through binding to EDN1 promoter and upregulating EDN1 expression.