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Novel Role of 5-Methyl-(6S)-Tetrahydrofolate in Mediating Endothelial Cell Tetrahydrobiopterin in Pregnancy and Implications for Gestational Hypertension.
Hypertension
September 2024
Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, Radcliffe Department of Medicine (Y.D., G.D., K.M.C., S.C.).
Background: Folate intake during pregnancy is essential for fetal development and maternal health. However, the specific effects of folic acid (FA) and 5-methyl-(6S)-tetrahydrofolate (5-MTHF) on the prevention and treatment of hypertensive disorders of pregnancy remain unclear. We investigated whether FA and 5-MTHF have different effects on endothelial cell tetrahydrobiopterin (BH4) metabolism in pregnancy and the possible consequences for endothelial NO generation, maternal blood pressure, and fetal growth.
View Article and Find Full Text PDFChronic Administration of Red Yeast Rice Mitigates Endothelial Dysfunction in Spontaneously Hypertensive Rats by Inhibiting Oxidative Stress and Endothelial Nitric Oxide Synthase Uncoupling.
Curr Vasc Pharmacol
October 2024
M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor, Malaysia.
Background: Hypertension is associated with endothelial dysfunction. An imbalance in the production of Nitric Oxide (NO) and Reactive Oxygen Species (ROS), leading to impaired NO-cyclic Guanosine Monophosphate (cGMP) pathway, contributes to this disorder. Red Yeast Rice (RYR), produced from the fermentation of rice with Monascus purpureus, is a traditional functional food originating from China.
View Article and Find Full Text PDFInternational consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis.
Autophagy
June 2024
Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA.
Article Synopsis
- - Macroautophagy is a complex process that can lead to cell death, influenced by various cell types and stressors, while ferroptosis is a specific kind of cell death related to lipid damage and iron dependency.
- - Certain types of autophagy, like ferritinophagy and lipophagy, play a role in triggering ferroptotic cell death by degrading protective proteins, whereas others, such as reticulophagy, help protect cells from this damage.
- - The review seeks to clarify the relationship between autophagy and ferroptosis, focusing on defining terms, outlining key components, discussing experimental techniques, and providing interpretation guidelines for ongoing research.
Reversal of Pulmonary Hypertension in a Human-Like Model: Therapeutic Targeting of Endothelial DHFR.
Circ Res
February 2024
Division of Molecular Medicine, Department of Anesthesiology, Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (P.M., Y.Z., Y.H., N.C.Z., J.Y.Y., H.C.).
Background: Pulmonary hypertension (PH) is a progressive disorder characterized by remodeling of the pulmonary vasculature and elevated mean pulmonary arterial pressure, resulting in right heart failure.
Methods: Here, we show that direct targeting of the endothelium to uncouple eNOS (endothelial nitric oxide synthase) with DAHP (2,4-diamino 6-hydroxypyrimidine; an inhibitor of GTP cyclohydrolase 1, the rate-limiting synthetic enzyme for the critical eNOS cofactor tetrahydrobiopterin) induces human-like, time-dependent progression of PH phenotypes in mice.
Results: Critical phenotypic features include progressive elevation in mean pulmonary arterial pressure, right ventricular systolic blood pressure, and right ventricle (RV)/left ventricle plus septum (LV+S) weight ratio; extensive vascular remodeling of pulmonary arterioles with increased medial thickness/perivascular collagen deposition and increased expression of PCNA (proliferative cell nuclear antigen) and alpha-actin; markedly increased total and mitochondrial superoxide production, substantially reduced tetrahydrobiopterin and nitric oxide bioavailabilities; and formation of an array of human-like vascular lesions.
Dihydropteridine Reductase Deficiency - A Rare and Potentially Treatable Cause Mimicking Cerebral Palsy.
Endocr Metab Immune Disord Drug Targets
November 2023
Unidade de Neuropediatria, Área de Pediatria, Centro Hospitalar Universitário de Lisboa Central.
Article Synopsis
- Dihydropteridine reductase deficiency (DHPRD) is a rare genetic disorder affecting the regeneration of tetrahydrobiopterin, leading to symptoms that often resemble cerebral palsy, such as developmental delays and feeding difficulties.
- A 2-year-old boy diagnosed with cerebral palsy in Guinea was found to have hyperphenylalaninemia, prompting further testing that revealed DHPRD due to a specific genetic variant.
- Early treatment initiation, including a restrictive diet and medication, led to moderate improvement in the child's condition, highlighting the importance of accurate diagnosis to ensure effective management of neurological disorders that may mimic cerebral palsy.
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