Tetrahydrobiopterin (BH4) functions as a cofactor for several important enzyme systems, and considerable evidence implicates BH4 as a key regulator of endothelial nitric oxide synthase (eNOS) in the setting of cardiovascular health and disease. BH4 bioavailability is determined by a balance of enzymatic de novo synthesis and recycling, versus degradation in the setting of oxidative stress. Augmenting vascular BH4 levels by pharmacological supplementation has been shown in experimental studies to enhance NO bioavailability. However, it has become more apparent that the role of BH4 in other enzymatic pathways, including other NOS isoforms and the aromatic amino acid hydroxylases, may have a bearing on important aspects of vascular homeostasis, inflammation, and cardiac function. This article reviews the role of BH4 in cardiovascular development and homeostasis, as well as in pathophysiological processes such as endothelial and vascular dysfunction, atherosclerosis, inflammation, and cardiac hypertrophy. We discuss the therapeutic potential of BH4 in cardiovascular disease states and attempt to address how this modulator of intracellular NO-redox balance may ultimately provide a powerful new treatment for many cardiovascular disea...Continue Reading
Distribution of 4a-hydroxytetrahydropterin dehydratase in rat tissues. Comparison with the aromatic amino acid hydroxylases
Macrophage nitric oxide synthase: relationship between enzyme-bound tetrahydrobiopterin and synthase activity
Tetrahydrobiopterin, a cofactor for rat cerebellar nitric oxide synthase, does not function as a reactant in the oxygenation of arginine
Some metabolic relationships between biopterin and folate: implications for the "methyl trap hypothesis"
Microtiter plate assay for the measurement of glutathione and glutathione disulfide in large numbers of biological samples
Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: precursors and role of the respiratory burst
Biosynthesis and metabolism of pterins in peripheral blood mononuclear cells and leukemia lines of man and mouse
Tetrahydrobiopterin biosynthesis. Studies with specifically labeled (2H)NAD(P)H and 2H2O and of the enzymes involved
Conversion of L-tyrosine to 3,4-dihydroxyphenylalanine by cell-free preparations of brain and sympathetically innervated tissues
On the presence of sepiapterin reductase different from folate and dihydrofolate reductase in chicken liver
Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation
Biosynthesis of tetrahydrobiopterin by de novo and salvage pathways in adrenal medulla extracts, mammalian cell cultures, and rat brain in vivo
Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine
Modulation of nitric oxide synthase activity in intact cells by intracellular tetrahydrobiopterin levels
Regulation of nitric oxide synthesis by proinflammatory cytokines in human umbilical vein endothelial cells. Elevations in tetrahydrobiopterin levels enhance endothelial nitric oxide synthase specific activity
Macrophage NO synthase: characterization of isolated oxygenase and reductase domains reveals a head-to-head subunit interaction
Targeted disruption of the tyrosine hydroxylase locus results in severe catecholamine depletion and perinatal lethality in mice.
Mutation of N-myristoylation site converts endothelial cell nitric oxide synthase from a membrane to a cytosolic protein
Involvement of nitric oxide in the endothelium-dependent relaxation induced by hydrogen peroxide in the rabbit aorta
Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development
Inducible nitric oxide synthase: identification of amino acid residues essential for dimerization and binding of tetrahydrobiopterin
Inhibition of tetrahydrobiopterin synthesis reduces in vivo nitric oxide production in experimental endotoxic shock
Neuronal nitric oxide synthase, a modular enzyme formed by convergent evolution: structure studies of a cysteine thiolate-liganded heme protein that hydroxylates L-arginine to produce NO. as a cellular signal
Endothelial nitric-oxide synthase. Expression in Escherichia coli, spectroscopic characterization, and role of tetrahydrobiopterin in dimer formation.
Cigarette smoking potentiates endothelial dysfunction of forearm resistance vessels in patients with hypercholesterolemia. Role of oxidized LDL
Endothelial function does not improve with high-intensity continuous exercise training in SHR: implications of eNOS uncoupling
Role for Tetrahydrobiopterin in the Fetoplacental Endothelial Dysfunction in Maternal Supraphysiological Hypercholesterolemia
Human Ischemic Cardiomyopathy Shows Cardiac Nos1 Translocation and its Increased Levels are Related to Left Ventricular Performance
Inflammation, oxidative stress, and cardiovascular disease risk factors in adults with cystic fibrosis
Effects of inorganic nitrate and beetroot supplementation on endothelial function: a systematic review and meta-analysis
Jak2/Stat1 pathway mediated tetrahydrobiopterin up-regulation contributes to nitric oxide overproduction in high-glucose cultured rat mesangial cells
Enhanced nitric oxide generation from nitric oxide synthases as the cause of increased peroxynitrite formation during acute restraint stress: Effects on carotid responsiveness to angiotensinergic stimuli in type-1 diabetic rats
Impaired systemic tetrahydrobiopterin bioavailability and increased dihydrobiopterin in adult falciparum malaria: association with disease severity, impaired microvascular function and increased endothelial activation
Protein Inhibitor of NOS1 Plays a Central Role in the Regulation of NOS1 Activity in Human Dilated Hearts
Endothelial cell metabolism: A novel player in atherosclerosis? Basic principles and therapeutic opportunities
L-Arginine and B vitamins improve endothelial function in subjects with mild to moderate blood pressure elevation
Tetrahydrobiopterin redox cycling in nitric oxide synthase: evidence supports a through-heme electron delivery
Computational analysis of interactions of oxidative stress and tetrahydrobiopterin reveals instability in eNOS coupling
GCH1 attenuates cardiac autonomic nervous remodeling in canines with atrial-tachypacing via tetrahydrobiopterin pathway regulated by microRNA-206
Tetrahydrobiopterin oral therapy recouples eNOS and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs
Failure of Isoflurane Cardiac Preconditioning in Obese Type 2 Diabetic Mice Involves Aberrant Regulation of MicroRNA-21, Endothelial Nitric-oxide Synthase, and Mitochondrial Complex I
Stay in Shape With BH4: Loss of Endothelial Tetrahydrobiopterin Promotes Aortic Aneurysm Development in Mice
Tetrahydrobiopterin Protects Against Hypertrophic Heart Disease Independent of Myocardial Nitric Oxide Synthase Coupling
Endothelial Nitric Oxide Synthase-Derived Nitric Oxide Prevents Dihydrofolate Reductase Degradation via Promoting S-Nitrosylation
New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease
L-Arginine and tetrahydrobiopterin supported nitric oxide production is crucial for the microbicidal activity of neutrophils
QDPR homologues in Danio rerio regulate melanin synthesis, early gliogenesis, and glutamine homeostasis
PPARδ agonist prevents endothelial dysfunction via induction of dihydrofolate reductase gene and activation of tetrahydrobiopterin salvage pathway
Pathobiology of ischiocavernosus and bulbospongiosus muscles in long-term diabetic male rats and its implication on erectile dysfunction.
Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease
The Relationship Between Homocysteine, Blood Pressure Variability, and Left Ventricular Hypertrophy in Patients with Essential Hypertension: An Observational Study
Say NO to ROS: Their Roles in Embryonic Heart Development and Pathogenesis of Congenital Heart Defects in Maternal Diabetes
Combined l-citrulline and tetrahydrobiopterin therapy improves NO signaling and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs.
Monomeric human soluble CD4 dimerizes at physiological temperature: VTSAXS data based modeling and screening of retardant molecules.
Neopterin derivatives - a novel therapeutic target rather than biomarker for atherosclerosis and related diseases.
Cardiovascular Disease Pathophysiology
Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.
Cardiomegaly, known as an enlarged heart, is a multifactorial disease with different pathophysiological mechanisms. Hypertension, pregnancy, exercise-induced and idiopathic causes are some mechanisms of cardiomegaly. Discover the latest research of cardiomegaly here.
Inflammation plays a significant role in the development of cardiovascular diseases, an understanding of these endogenous processes is critical for evaluating the risks and potential treatment strategies. Discover the latest research on cardiovascular inflammation here.
Atherosclerosis Disease Progression
Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.