Maternal supraphysiological hypercolesterolemia leads to endothelial dysfunction of the human fetoplacental macro and microvasculature

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dc.contributor.authorLeiva, Andrea
dc.contributor.authorSalsoso, Rocío
dc.contributor.authorSáez, Tamara
dc.contributor.authorSilva, Luis
dc.contributor.authorSanhueza, Carlos
dc.contributor.authorPardo, Fabian
dc.contributor.authorSobrevía, Luis
dc.date.accessioned2017-06-21T20:53:01Z
dc.date.available2017-06-21T20:53:01Z
dc.date.issued2015
dc.description.abstractMaternal physiological hypercholesterolemia (MPH) occurs in pregnancy assuring fetal growth and development. However, maternal supraphysiological hypercholesterolemia (MSPH) leads to increased atherosclerosis in the fetal vasculature. In this study the maternal and neonatal total cholesterol (TCh) and lipoprotein levels were determined in a group of pregnant women and her newborns. A cut-off value for MSPH was established as maternal TCh levels at term of pregnancy >280 mg/dl. Pregnancies with values over this cut-off point were associated with fetoplacental endothelial dysfunction evaluated as reduced endothelial-dependent vascular dilation in the macro- (umbilical vein; 41 ± 7% and 10± 2% for MPH and MSPH, respectively) and microvasculature (veins in placental stem villi; 52 ± 6% and 1± 0.2% for MPH and MSPH, respectively). The mechanisms involved in this phenomenon include reduced nitric oxide synthase (NOS) activity and therefore reduced nitric oxide (NO) availability in human umbilical vein endothelial cells (HUVEC; reduction of 51 ± 2% compared with MPH) and human placental microvascular endothelial cells (HPMEC; reduction of 83 ± 4% compared with MPH). MSPH was also associated with reduced synthesis of the eNOS cofactor tetrahydrobiopterin (BH4; reduction of 87.5 ± 5% compared with MPH) as well as increased activity of arginases, a group of enzymes that compete with NOS for the substrate L-arginine (1.5 times compared with MPH). Interestingly, the restoration of the BH4 levels and the inhibition of arginases improved the endothelial function impaired by the MSPH condition. Therefore MSPH is a maternal condition likely involved in the endothelial dysfunction and the later development of atherosclerosis described for MSPH offspring. However, the mechanism(s) leading to the development MSPH as well as whether this maternal condition modifies the placental transport of cholesterol and therefore the fetal lipid function are actually unknown.
dc.identifier.citationPlacenta, 2015, vol. 36, n° 4, p. 487-487
dc.identifier.urihttp://hdl.handle.net/11447/1451
dc.identifier.urihttp://hdl.handle.net/11447/651
dc.identifier.urihttp://dx.doi.org/10.1016/j.placenta.2015.01.441
dc.language.isoen_US
dc.subjectPregnancy
dc.subjectCholesterol
dc.titleMaternal supraphysiological hypercolesterolemia leads to endothelial dysfunction of the human fetoplacental macro and microvasculature
dc.typeArtículo

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