A5043916843- Folate and B Vitamins Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nitric Oxide and Endothelin Effects
- Atherosclerosis and Cardiovascular Diseases
- COVID-19 Clinical Research Studies
- Sulfur Compounds in Biology
- Blood Coagulation and Thrombosis Mechanisms
- Pregnancy and preeclampsia studies
- Venous Thromboembolism Diagnosis and Management
- Liver Disease and Transplantation
- Iron Metabolism and Disorders
- Eicosanoids and Hypertension Pharmacology
- Adipokines, Inflammation, and Metabolic Diseases
- Antiplatelet Therapy and Cardiovascular Diseases
- Endoplasmic Reticulum Stress and Disease
- Hemoglobinopathies and Related Disorders
- Metabolism and Genetic Disorders
- Liver Disease Diagnosis and Treatment
- Antioxidant Activity and Oxidative Stress
- Trace Elements in Health
- Renin-Angiotensin System Studies
- Organ Transplantation Techniques and Outcomes
- Fluoride Effects and Removal
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Inflammasome and immune disorders
University of Iowa
2015-2024
Fraternal Order of Eagles
2024
Iowa City VA Health Care System
2022-2024
University of Iowa Health Care
2018-2023
University of Iowa Hospitals and Clinics
2022-2023
Sunan Kalijaga State Islamic University Yogyakarta
2012-2018
Bloodworks Northwest
2015
University of Washington
2015
Veterans Health Administration
2001-2008
Baylor University
2002-2005
Hepatic steatosis is common in patients having severe hyperhomocysteinemia due to deficiency for cystathionine β-synthase. However, the mechanism by which homocysteine promotes development and progression of hepatic unknown. We report here that homocysteine-induced endoplasmic reticulum (ER) stress activates both unfolded protein response sterol regulatory element–binding proteins (SREBPs) cultured human hepatocytes as well vascular endothelial aortic smooth muscle cells. Activation SREBPs...
Alzheimer's disease (AD) neuropathology is characterized by the accumulation of phosphorylated tau and amyloid-β peptides derived from amyloid precursor protein (APP). Elevated blood levels homocysteine are a significant risk factor for many age-related diseases, including AD. Impaired metabolism favors formation S -adenosylhomocysteine, leading to inhibition methyltransferase-dependent reactions. Here, we show that incubation neuroblastoma cells with -adenosylhomocysteine results in reduced...
Abstract —Hyperhomocysteinemia is associated with increased risk for cardiovascular events, but it not certain whether a mediator of vascular dysfunction or marker another factor. Homocysteine levels are regulated by folate bioavailability and also the methyl donor S -adenosylmethionine (SAM) its metabolite -adenosylhomocysteine (SAH). We tested hypotheses that endothelial occurs in hyperhomocysteinemic mice absence deficiency SAM SAH altered dysfunction. Heterozygous cystathionine...
Background— The incidence of thrombotic events increases during aging, but the mechanisms are not well understood. To investigate prothrombotic role oxidative stress we tested hypothesis that aged mice overexpressing antioxidant enzyme glutathione peroxidase-1 (Gpx1) protected from experimental thrombosis. Methods and Results— Susceptibility to carotid artery thrombosis was first examined in wild-type C57BL/6J mice. After photochemical injury artery, time stable occlusion significantly...
Cisplatin contributes to acute kidney injury (AKI) and chronic disease (CKD) that occurs with greater frequency severity in older patients. Age-associated cisplatin sensitivity human fibroblasts involves increased mitochondrial superoxide produced by donor cells.
Background and Purpose— Hyperhomocysteinemia is an emerging risk factor for stroke, but little known about effects of hyperhomocysteinemia on cerebral vascular function. We tested the hypothesis that chronic in mice causes endothelial dysfunction arterioles through a mechanism involves superoxide. Methods— Mice heterozygous targeted disruption cystathionine β-synthase gene ( Cbs +/−) their wild type littermates +/+) were fed either control diet or high-methionine 10 to 12 months. Results—...
A causal relation between hyperhomocysteinemia (HHcy) and accelerated atherosclerosis has been established in apolipoprotein E-deficient (apoE-/-) mice. Although several cellular stress mechanisms have proposed to explain the atherogenic effects of HHcy, including oxidative stress, endoplasmic reticulum (ER) inflammation, their association with atherogenesis not completely elucidated.ApoE-/- mice were fed a control or high-methionine (HM) diet for 4 (early lesion group) 18 (advanced weeks...
This study investigated the direct roles of hydrogen peroxide (H
Objective— We tested the hypothesis that deficiency of cellular glutathione peroxidase (GPx-1) enhances susceptibility to endothelial dysfunction in mice with moderate hyperhomocysteinemia. Methods and Results— Mice were wild type ( Gpx1 +/+ ), heterozygous +/− or homozygous −/− ) for mutated allele fed a control diet high-methionine 17 weeks. Plasma total homocysteine was elevated on compared (23±3 versus 6±0.3 μmol/L, respectively; P <0.001) not influenced by genotype. In diet, maximal...
Hyperhomocysteinemia is a risk factor for stroke, myocardial infarction, and venous thrombosis. Moderate hyperhomocysteinemia associated with impaired endothelial function, but the mechanisms responsible dysfunction in are poorly understood. We have used genetic dietary approaches to produce mice. Heterozygous cystathionine beta-synthase-deficient mice (CBS +/-), which selective defect homocysteine transsulfuration, wild-type +/+) littermates were fed either control diet or that relatively...
Elevated plasma levels of homocysteine are a risk factor for cardiovascular diseases, neural tube defects, and Alzheimer's disease. The transsulfuration pathway converts to cysteine, approximately 50% the cysteine in glutathione is derived from human liver cells, which suggests hypothesis that defects perturb redox homeostasis. To test this hypothesis, we examined murine model hyperhomocysteinemia gene encoding first enzyme pathway, cystathionine beta-synthase (CBS), has been disrupted....
Levels of reactive oxygen species, including hydrogen peroxide(,) increase in blood vessels during hypertension and response to angiotensin II (Ang II). Although glutathione peroxidases are known metabolize peroxide, the role peroxidase is poorly defined. We tested hypothesis that peroxidase-1 protects against Ang II-induced endothelial dysfunction. Responses carotid arteries from Gpx1-deficient (Gpx1(+/-) Gpx1(-/-)) Gpx1 transgenic mice, their respective littermate controls, were examined...
We tested the hypothesis that pathogenesis of alcoholic liver injury is mediated by epigenetic changes in regulatory genes result from induction aberrant methionine metabolism ethanol feeding. Five-month-old cystathionine beta synthase heterozygous and wild-type C57BL/6J littermate mice were fed liquid control or diets intragastric infusion for 4 weeks. Both ethanol-fed groups showed typical histopathology steatohepatitis, with reduction S -adenosylmethionine (SAM), elevation...
Abstract Deficiency of the Nox2 (gp91phox) catalytic subunit nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a genetic cause X-linked chronic granulomatous disease, condition in which patients are prone to infection resulting from loss oxidant production by neutrophils. Some studies have suggested role for superoxide derived NADPH platelet activation and thrombosis, but data conflicting. Using rigorous comprehensive approach, we tested hypothesis that deficiency attenuates...
Reactive oxygen species (ROS) contribute to platelet hyperactivation during aging. Several oxidative pathways and antioxidant enzymes have been implicated; however, their mechanistic contributions aging remain elusive. We hypothesized that mitochondria are an important source of ROS mitochondrial SOD2 (superoxide dismutase) protects against ROS-driven activation thrombosis
Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, has been proposed to be a mediator vascular dysfunction during hyperhomocysteinemia. Levels ADMA are regulated by dimethylaminohydrolase (DDAH). Using both in vitro and vivo approaches, we tested the hypothesis that hyperhomocysteinemia causes downregulation two genes encoding DDAH ( Ddah1 Ddah2). In MS-1 murine endothelial cell line, addition homocysteine decreased NO production but did not elevate or...
Hyperhomocysteinemia is a risk factor for cardiovascular disease and stroke. Like many other factors, hyperhomocysteinemia produces endothelial dysfunction due to impaired bioavailability of endothelium-derived nitric oxide (NO). The molecular mechanisms responsible decreased NO bioavailabil ity in are incompletely understood, but emerging evidence suggests that asymmetric dimethylarginine (ADMA), an endogenous inhibitor synthase, may be key mediator. Homocysteine produced during the...
Background— Methionine synthase (MS) catalyzes the folate-dependent remethylation of homocysteine to methionine. We tested hypothesis that deficiency MS impairs endothelial function in mice heterozygous for disruption Mtr gene, which encodes MS. Methods and Results— Plasma total was similar wild-type ( +/+ ) +/− fed a control diet (4.5±0.3 5.3±0.4 μmol/L, respectively) mildly elevated low-folate (LF) (7.5±0.7 9.6±1.2 respectively; P <0.001 versus diet). Dilatation cerebral arterioles...