title: Equilibrative nucleoside transporters in fetal endothelial dysfunction in diabetes mellitus and hyperglycaemia.
abstract: Diabetes mellitus types 1 and 2, and gestational diabetes are characterized by abnormal D-glucose metabolism and hyperglycaemia, and induce foetal endothelial dysfunction with implications in adult life increasing the risk of vascular diseases. Synthesis of nitric oxide (NO) and uptake of L-arginine (i.e. the L-arginine/NO signalling pathway) and adenosine (a vasoactive endogenous nucleoside) by the umbilical vein endothelium is altered in pathological pregnancies, including pregnancies with pre-established diabetes mellitus or in gestational diabetes. The mechanisms underlying these alterations include differential expression of equilibrative nucleoside transporters (ENTs), amino acid transporters and NO synthases (NOS). Modulation of ENTs and NOS expression and activity in endothelium involves several signalling molecules, including protein kinase C, mitogen-activated protein kinases p42 and p44, calcium and phosphatidyl inositol 3 kinase. Elevated extracellular D-glucose and diabetes alters human endothelial function. However, information regarding modulation the transport capacity as well as expression of ENTs is limited. This review focuses on the effect of diabetes mellitus and gestational diabetes, and hyperglycaemia on the reported mechanisms described for transcriptional and post-transcriptional regulation of ENTs, and the potential consequences for foetal endothelial function in these pathologies. Recent available information regarding functional consequences of an abnormal environment on the functionality of the endothelium from microvasculature of the human placenta is mentioned. The available information is scarce, but it could contribute to a better understanding of the cell and molecular basis of the altered vascular endothelial function in this pathological conditions, emphasizing the key role of this type of epithelium in fetal-placental function and the normal foetal development and growth.
authors.affiliation: Cellular and Molecular Physiology Laboratory, Department of Obstetrics and Gynaecology, Medical Research Centre, School of Medicine, Pontificia Universidad Católica de Chile, P.O. Box 114-D, Santiago, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Westermeier
authors.forename: Carlos
authors.initials: C
authors.lastname: Puebla
authors.forename: José Luis
authors.initials: JL
authors.lastname: Vega
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farías
authors.forename: Carlos
authors.initials: C
authors.lastname: Escudero
authors.forename: Paola
authors.initials: P
authors.lastname: Casanello
authors.forename: Luis
authors.initials: L
authors.lastname: Sobrevia
mesh_terms: D000328:Adult; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D016640:Diabetes, Gestational / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D033705:Equilibrative Nucleoside Transport Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy
chemical_list: D033705:Equilibrative Nucleoside Transport Proteins