High glucose induces dysfunction of human umbilical vein endothelial cells by upregulating miR-137 in gestational diabetes mellitus

• Published in: Microvascular research 2018-07, Vol.118, p.90-100
• Main Authors: Peng, Hai-Yan, Li, Hua-Ping, Li, Ming-Qing
• Format: Article
• Language: English
• Subjects: Adult; Blood Glucose - metabolism; Case-Control Studies; Cell Adhesion - drug effects; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Chemotaxis - drug effects; Coculture Techniques; Cytokines - genetics; Cytokines - metabolism; Diabetes, Gestational - blood; Diabetes, Gestational - genetics; Diabetes, Gestational - metabolism; Diabetes, Gestational - pathology; Female; Gestational diabetes mellitus (GDM); Glucose - toxicity; High glucose (HG); Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Human Umbilical Vein Endothelial Cells - pathology; Humans; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; miR-137; Monocyte; Neovascularization, Pathologic; Pregnancy; THP-1 Cells; U937 Cells; Up-Regulation; Vascular endothelial cells (VECs); Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0026-2862; 1095-9319
• DOI: 10.1016/j.mvr.2018.03.002

Recent studies have revealed considerable dysfunction of vascular endothelial cells (VECs) and abnormal expression of microRNA (miR)-137 in women with gestational diabetes mellitus (GDM), and the aim of this study was to clarify the underlying mechanism and possible role of microRNA (miR)-137 in dysfunction of VECs during GDM. We found increased levels of miR-137 in the plasma of GDM women and high-glucose (HG)-exposed HUVECs. Upregulating miR-137 in HUVECs elevated the chemokine (C-C motif) ligand 2 (CCL2) secretion and enhanced the chemotaxis and adhesion of U937 and THP-1 (two human acute monocytic leukemia cell lines) cells to HUVECs in a co-culture system. Moreover, HG stimulation and/or overexpression of miR-137 inhibited the viability, upregulated the expression levels of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), E-selectin, and inflammatory cytokine interleukin (IL)-6, and downregulated the production of IL-8, vascular endothelial growth factor (VEGF), and angiogenesis of HUVECs in vitro. These results imply that up-regulated miR-137 by HG can restrict the viability and angiogenesis, promote the activation and inflammatory cytokine secretion of VECs, and stimulate the monocyte chemotaxis and adhesion to VECs. Ultimately, we have concluded that miR-137 is crucial to HG-induced VEC dysfunction and may be involved in pathology of GDM. •High level of miR-137 was found in gestational diabetes mellitus (GDM) women;•Upregulating miR-137 enhanced the interaction between endothelial cells and monocytes;•miR-137 might play a role in GDM-induced endothelial celsl dysfunction.