A5070640404- Blood Coagulation and Thrombosis Mechanisms
- Folate and B Vitamins Research
- Platelet Disorders and Treatments
- Hemophilia Treatment and Research
- Venous Thromboembolism Diagnosis and Management
- Nitric Oxide and Endothelin Effects
- Atherosclerosis and Cardiovascular Diseases
- Cell Adhesion Molecules Research
- Esophageal and GI Pathology
- Protease and Inhibitor Mechanisms
- Blood groups and transfusion
- Complement system in diseases
- Iron Metabolism and Disorders
- Metabolism and Genetic Disorders
- Sulfur Compounds in Biology
- Antiplatelet Therapy and Cardiovascular Diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Pregnancy and preeclampsia studies
- Hemostasis and retained surgical items
- COVID-19 Clinical Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Chronic Myeloid Leukemia Treatments
- Atrial Fibrillation Management and Outcomes
- Heparin-Induced Thrombocytopenia and Thrombosis
- Lipoproteins and Cardiovascular Health
University of Iowa
2016-2025
University of Iowa Hospitals and Clinics
2010-2021
University of Iowa Health Care
2018
National Cerebral and Cardiovascular Center
2017
Creative Commons
2016
University of North Carolina at Chapel Hill
2001-2015
Centers for Disease Control and Prevention
2014-2015
Harvard University
2006-2015
Bloodworks Northwest
2015
University of Washington
2015
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...
Elevated plasma homocyst(e)ine may predispose to complications of vascular disease. Homocysteine alters vasomotor regulatory and anticoagulant properties cultured endothelial cells, but little is known about effects hyperhomocyst(e)inemia on function in vivo. We tested the hypothesis that diet-induced moderate associated with dysfunction cynomolgus monkeys. Plasma increased from 4.O +/- O.2 microM when monkeys were fed normal diet 10.6 2.6 they modified (mean SE; P = 0.02). Vasomotor...
Elevated levels of plasma homocysteine are associated with both venous and arterial thrombosis. Homocysteine inhibits the function thrombomodulin, an anticoagulant glycoprotein on endothelial surface that serves as a cofactor for activation protein C by thrombin. The effects thrombomodulin expression were investigated in cultured human umbilical vein cells CV-1(18A) express recombinant thrombomodulin. Addition 5 mM to produced slight increases mRNA synthesis without affecting cell viability....
The glycolytic enzyme PKM2 (pyruvate kinase muscle 2) is upregulated in monocytes/macrophages of patients with atherosclerotic coronary artery disease. However, the role cell type-specific setting atherosclerosis remains to be defined. We determined whether myeloid cell-specific regulates efferocytosis and atherosclerosis.
Abstract —Hyperhomocyst(e)inemia is associated with endothelial dysfunction. Mechanisms responsible for dysfunction in hyperhomocyst(e)inemia may involve impaired bioavailability of endothelium-dependent nitric oxide. We tested the hypothesis that an elevated plasma concentration asymmetric dimethylarginine (ADMA), endogenous inhibitor oxide synthase. One group adult cynomolgus monkeys was fed either a control or hyperhomocyst(e)inemic diet 4 weeks randomized crossover design. The second...
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...
Hyperhomocyst(e)inaemia is associated with endothelial dysfunction in animals and humans. Mechanisms responsible for hyperhomocyst(e)inaemia are poorly understood, but may involve impaired bioavailability of endothelium-derived nitric oxide (NO). We hypothesized that acute elevation homocyst(e)ine by oral methionine loading stimulate the formation asymmetrical dimethylarginine (ADMA), an endogenous inhibitor NO synthase, due to a transmethylation reaction during from methionine. studied nine...
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...
The primary translation product of human intestinal apolipoprotein A-I mRNA was isolated from wheat germ and ascites cell-free systems.Comparison its NHz-terminal sequence with that plasma high density lipoprotein-associated showed it is initially synthesized as a preproprotein.Like rat preproapolipoprotein A-I, contains an 18-amino acid prepeptide 6-amino propeptide.The highly unusual COOH-terminal Gln-Gln dipeptide present in the pro-segment also represented at same position sequence.The...
Normal D-dimer levels after withdrawal of anticoagulant therapy are associated with a reduced risk for recurrence in patients unprovoked venous thromboembolism (VTE) and may justify stopping treatment.To determine whether first VTE negative test result who stop have low recurrence.Prospective management study blinded outcome assessment. (ClinicalTrials.gov: NCT00720915).13 university-affiliated clinical centers.410 adults aged 75 years or younger proximal deep thrombosis pulmonary embolism...
Summary Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels less frequent injections compared standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety clinical efficacy N8-GP when administered prophylaxis, previously treated aged ≥12 years severe A....
The adapter protein SLP-76 is expressed in T lymphocytes and hematopoietic cells of the myeloid lineage, known to be a substrate tyrosine kinases that are activated after ligation T-cell antigen receptor. Transient overexpression line potentiates transcriptional activation receptor ligation, while loss expression abrogates several receptor-dependent signaling pathways. Mutant mice lack manifest severe block at an early stage thymocyte development, implicating events promote maturation. While...
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—...