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.
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http://dx.doi.org/10.1161/ATVBAHA.113.301987 | DOI Listing |
Clin Appl Thromb Hemost
January 2025
Hemostasis and Thrombosis Research Laboratories, Loyola University Medical Center, Maywood, Illinois, USA.
Introduction: Persistent elevation of biomarkers associated with endothelial dysfunction in convalescent COVID-19 patients has been linked to an increased risk of long-term cardiovascular complications, including long COVID syndrome. Sulodexide, known for its vascular endothelial affinity, has demonstrated pleiotropic protective properties. This study aims to evaluate the impact of sulodexide on serum levels of endothelial dysfunction biomarkers in patients during the convalescent phase of COVID-19.
View Article and Find Full Text PDFMed Sci Monit
January 2025
Department of Obstetrics and Gynecology, Padjadjaran University, Bandung, West Java, Indonesia.
BACKGROUND Urinary tract infections (UTIs) are common during pregnancy and can negatively impact maternal and neonatal health. Hypertension in pregnancy is a leading cause of maternal morbidity. UTIs can contribute to hypertension development through mechanisms like inflammation, leading to endothelial dysfunction and impaired placental development.
View Article and Find Full Text PDFCardiovasc Diabetol
January 2025
Department of Clinical Pharmacy, School of Preclinical Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tong jia Lane, Nanjing, 210009, People's Republic of China.
Background: Inflammatory diseases impair the reparative properties of endothelial progenitor cells (EPC); however, the involvement of diabetes in EPC dysfunction associated with myocardial infarction (MI) remains unknown.
Methods: A model was established combining high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice with myocardial infarction. The therapeutic effects of transplanted wild-type EPC, Nlrp3 knockout EPC, and Nlrp3 overexpression EPC were evaluated.
Exp Mol Med
January 2025
Department of Physiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
Hemophilia A (HA) is caused by mutations in coagulation factor VIII (FVIII). Genome editing in conjunction with patient-derived induced pluripotent stem cells (iPSCs) is a promising cell therapy strategy, as it replaces dysfunctional proteins resulting from genetic mutations with normal proteins. However, the low expression level and short half-life of FVIII still remain significant limiting factors in the efficacy of these approaches in HA.
View Article and Find Full Text PDFHum Reprod
January 2025
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Study Question: Is elevated plasma molybdenum level associated with increased risk for idiopathic premature ovarian insufficiency (POI)?
Summary Answer: Elevated plasma molybdenum level is associated with an increased risk of idiopathic POI through vascular endothelial injury and inhibition of granulosa cell proliferation.
What Is Known Already: Excessive molybdenum exposure has been associated with ovarian oxidative stress in animals but its role in the development of POI remains unknown.
Study Design, Size, Duration: Case-control study of 30 women with idiopathic POI and 31 controls enrolled from August 2018 to May 2019.
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