Maternal supraphysiological hypercholesterolemia leads to reduced nitric oxide synthase activity associated with reduced levels of tetrahydrobiopterin in huvec

Leiva, Andrea; Fuenzalida, Bárbara; Sobrevia, Bastián; Pardo, Fabián; Sobrevía, Luis

doi:10.1016/j.atherosclerosis.2014.05.078

Cited by 2 publications

(1 citation statement)

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“…As a result, these potential mechanisms could explain the endothelial dysfunction and reduced vascular relaxation observed in MSPH. Preliminary results show that the BH 4 level is reduced in HUVECs from MSPH [ 88 ] (Leiva A., Sobrevia L., unpublished ). However, it is unknown whether BH 4 metabolism is altered in human fetoplacental endothelial cells in pregnancies with MSPH or whether restoration of the BH 4 level improves the endothelial dysfunction in MSPH [ 4 – 6 , 33 ].…”

Section: Bh 4 Metabolism In Msphmentioning

confidence: 99%

Role for Tetrahydrobiopterin in the Fetoplacental Endothelial Dysfunction in Maternal Supraphysiological Hypercholesterolemia

Leiva

Fuenzalida

Westermeier

et al. 2015

Oxidative Medicine and Cellular Longevity

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Maternal physiological hypercholesterolemia occurs during pregnancy, ensuring normal fetal development. In some cases, the maternal plasma cholesterol level increases to above this physiological range, leading to maternal supraphysiological hypercholesterolemia (MSPH). This condition results in endothelial dysfunction and atherosclerosis in the fetal and placental vasculature. The fetal and placental endothelial dysfunction is related to alterations in the L-arginine/nitric oxide (NO) pathway and the arginase/urea pathway and results in reduced NO production. The level of tetrahydrobiopterin (BH4), a cofactor for endothelial NO synthase (eNOS), is reduced in nonpregnant women who have hypercholesterolemia, which favors the generation of the superoxide anion rather than NO (from eNOS), causing endothelial dysfunction. However, it is unknown whether MSPH is associated with changes in the level or metabolism of BH4; as a result, eNOS function is not well understood. This review summarizes the available information on the potential link between MSPH and BH4 in causing human fetoplacental vascular endothelial dysfunction, which may be crucial for understanding the deleterious effects of MSPH on fetal growth and development.

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Section: Bh 4 Metabolism In Msphmentioning

confidence: 99%

Role for Tetrahydrobiopterin in the Fetoplacental Endothelial Dysfunction in Maternal Supraphysiological Hypercholesterolemia

Leiva

Fuenzalida

Westermeier

et al. 2015

Oxidative Medicine and Cellular Longevity

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Nitric Oxide is a Central Common Metabolite in Vascular Dysfunction Associated with Diseases of Human Pregnancy

Leiva

Fuenzalida²,

Barros³

et al. 2016

CVP

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Preeclampsia (PE), gestational diabetes mellitus (GDM), and maternal supraphysiological hypercholesterolaemia (MSPH) are pregnancy-related conditions that cause metabolic disruptions leading to alterations of the mother, fetus and neonate health. These syndromes result in fetoplacental vascular dysfunction, where nitric oxide (NO) plays a crucial role. PE characterizes by abnormal increase in the placental blood pressure and a negative correlation between NO level and fetal weight, suggesting that increased NO level and oxidative stress could be involved. GDM courses with macrosomia along with altered function of the fetal cardiovascular system and fetoplacental vasculature. Even when NO synthesis in the fetoplacental vasculature is increased, NO bioavailability is reduced due to the higher oxidative stress seen in this disease. In MSPH, there is an early development of atherosclerotic lesions in fetal and newborn arteries, altered function of the fetoplacental vasculature, and higher markers of oxidative stress in fetal blood and placenta, thus, vascular alterations related with NO metabolism occur as a consequence of this syndrome. Potential mechanisms of altered NO synthesis and bioavailability result from transcriptional and post-translational NO synthases (NOS) modulation, including phosphorylation/dephosphorylation cycles, coupling/uncoupling of NOS, tetrahydrobiopterin bioavailability, calcium/calmodulin-NOS and caveolin-1-NOS interaction. Additionally, oxidative stress also plays a role in the reduced NO bioavailability. This review summarizes the available information regarding lower NO bioavailability in these pregnancy pathologies. A common NO-dependent mechanism in PE, GDM and MSPH contributing to fetoplacental endothelial dysfunction is described.

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Maternal supraphysiological hypercholesterolemia leads to reduced nitric oxide synthase activity associated with reduced levels of tetrahydrobiopterin in huvec

Cited by 2 publications

References 0 publications

Role for Tetrahydrobiopterin in the Fetoplacental Endothelial Dysfunction in Maternal Supraphysiological Hypercholesterolemia

Role for Tetrahydrobiopterin in the Fetoplacental Endothelial Dysfunction in Maternal Supraphysiological Hypercholesterolemia

Nitric Oxide is a Central Common Metabolite in Vascular Dysfunction Associated with Diseases of Human Pregnancy

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