Maternal Hypercholesterolemia in Pregnancy Associates With Umbilical Vein Endothelial Dysfunction Role of Endothelial Nitric Oxide Synthase and Arginase II

Leiva, Andrea, Diez de Medina, Camila, Salsoso, Rocio, Saez, Tamara, San Martin, Sebastian, Abarzua, Fernando, Farias, Marcelo, Guzman-Gutierrez, Enrique, Pardo, Fabian and Sobrevia, Luis (2013) Maternal Hypercholesterolemia in Pregnancy Associates With Umbilical Vein Endothelial Dysfunction Role of Endothelial Nitric Oxide Synthase and Arginase II. Arteriosclerosis Thrombosis and Vascular Biology, 33 10: 2444-2453. doi:10.1161/ATVBAHA.113.301987


Author Leiva, Andrea
Diez de Medina, Camila
Salsoso, Rocio
Saez, Tamara
San Martin, Sebastian
Abarzua, Fernando
Farias, Marcelo
Guzman-Gutierrez, Enrique
Pardo, Fabian
Sobrevia, Luis
Title Maternal Hypercholesterolemia in Pregnancy Associates With Umbilical Vein Endothelial Dysfunction Role of Endothelial Nitric Oxide Synthase and Arginase II
Journal name Arteriosclerosis Thrombosis and Vascular Biology   Check publisher's open access policy
ISSN 1079-5642
1524-4636
Publication date 2013-10-01
Year available 2013
Sub-type Article (original research)
DOI 10.1161/ATVBAHA.113.301987
Open Access Status Not Open Access
Volume 33
Issue 10
Start page 2444
End page 2453
Total pages 10
Place of publication Philadelphia, PA United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
 Objective—Human pregnancy that courses with maternal supraphysiological hypercholesterolemia (MSPH) correlates with atherosclerotic lesions in fetal arteries. It is known that hypercholesterolemia associates with endothelial dysfunction in adults, a phenomenon where nitric oxide (NO) and arginase are involved. However, nothing is reported on potential alterations in the fetoplacental endothelial function in MSPH. The aim of this study was to determine whether MSPH alters fetal vascular reactivity via endothelial arginase/urea and L-arginine transport/NO signaling pathways.

Approach and Results—Total cholesterol <280 mg/dL was considered as maternal physiological hypercholesterolemia (n=46 women) and ≥280 mg/dL as MSPH (n=28 women). Maternal but not fetal total cholesterol and low-density lipoprotein-cholesterol levels were elevated in MSPH. Umbilical veins were used for vascular reactivity assays (wire myography), and primary cultures of umbilical vein endothelial cells to determine arginase, endothelial NO synthase (eNOS), and human cationic amino acid transporter 1 and human cationic amino acid transporter 2A/B expression and activity. MSPH reduced calcitonine gene–related peptide-umbilical vein relaxation and increased intima/media ratio (histochemistry), as well as reduced eNOS activity (L-citrulline synthesis from L-arginine, eNOS phosphorylation/dephosphorylation), but increased arginase activity and arginase II protein abundance. Arginase inhibition increased eNOS activity and L-arginine transport capacity without altering human cationic amino acid transporter 1 or human cationic amino acid transporter 2A/B protein abundance in maternal physiological hypercholesterolemia and MSPH.

Conclusions—MSPH is a pathophysiological condition altering umbilical vein reactivity because of fetal endothelial dysfunction associated with arginase and eNOS signaling imbalance. We speculate that elevated maternal circulating cholesterol is a factor leading to fetal endothelial dysfunction, which could have serious consequences to the growing fetus.

Keyword Arginase
Cholesterol
Endothelium
Nitric oxide
Pregnancy
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Faculty of Health and Behavioural Sciences -- Publications
UQ Centre for Clinical Research Publications
Official 2014 Collection
 
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