A5007944034- Hemoglobinopathies and Related Disorders
- Nitric Oxide and Endothelin Effects
- Hemoglobin structure and function
- Iron Metabolism and Disorders
- Pulmonary Hypertension Research and Treatments
- Erythrocyte Function and Pathophysiology
- Neuroscience of respiration and sleep
- Heme Oxygenase-1 and Carbon Monoxide
- Blood groups and transfusion
- Neonatal Health and Biochemistry
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cardiovascular Function and Risk Factors
- Eicosanoids and Hypertension Pharmacology
- Cardiac Ischemia and Reperfusion
- Folate and B Vitamins Research
- Epigenetics and DNA Methylation
- Renin-Angiotensin System Studies
- Transplantation: Methods and Outcomes
- Pregnancy and preeclampsia studies
- Genetic Associations and Epidemiology
- High Altitude and Hypoxia
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bone and Joint Diseases
- Electron Spin Resonance Studies
- Heart Failure Treatment and Management
University of Pittsburgh
2016-2025
University of Maryland, Baltimore
2022-2025
National Heart Lung and Blood Institute
2005-2024
University of Maryland, College Park
2024
University of Iowa
2024
Bayer (United States)
2024
Actelion (Switzerland)
2024
University of Baltimore
2023-2024
Acceleron Pharma (United States)
2024
Novartis (Switzerland)
2024
Abstract The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood sleep disorders, with ultimate goal improving diagnosis, treatment prevention these diseases. initial phases focused on whole-genome sequencing individuals rich phenotypic data diverse backgrounds. Here we describe TOPMed goals design as well available resources early insights obtained from sequence data. include a variant browser, genotype...
The prevalence of pulmonary hypertension in adults with sickle cell disease, the mechanism its development, and prospective prognostic significance are unknown.We performed Doppler echocardiographic assessments pulmonary-artery systolic pressure 195 consecutive patients (82 men 113 women; mean [+/-SD] age, 36+/-12 years). Pulmonary was prospectively defined as a tricuspid regurgitant jet velocity at least 2.5 m per second. Patients were followed for 18 months, data censored time death or...
Sickle cell disease is characterized by a state of nitric oxide resistance and limited bioavailability l-arginine, the substrate for synthesis. We hypothesized that increased arginase activity dysregulated arginine metabolism contribute to endothelial dysfunction, pulmonary hypertension, patient outcomes.To explore role in sickle pathogenesis, mortality.Plasma amino acid levels, plasma erythrocyte activities, hypertension status as measured Doppler echocardiogram were prospectively obtained...
Nitrite represents a circulating and tissue storage form of NO whose bioactivation is mediated by the enzymatic action xanthine oxidoreductase, nonenzymatic disproportionation, reduction deoxyhemoglobin, myoglobin, heme proteins. Because rate generation from nitrite linearly dependent on reductions in oxygen pH levels, we hypothesized that would be reduced to ischemic exert NO-dependent protective effects. Solutions sodium were administered setting hepatic cardiac ischemia-reperfusion (I/R)...
Previous studies have revealed a novel interaction between deoxyhemoglobin and nitrite to generate nitric oxide (NO) in blood. It has been proposed that acts as an endocrine reservoir of NO contributes hypoxic vasodilation signaling. Here, we characterize the reductase activity deoxymyoglobin, which reduces approximately 36 times faster than because its lower heme redox potential. We hypothesize physiologically this reaction releases proximity mitochondria regulates respiration through...
Background— Intravascular red cell hemolysis impairs nitric oxide (NO)–redox homeostasis, producing endothelial dysfunction, platelet activation, and vasculopathy. Red blood storage under standard conditions results in reduced integrity of the erythrocyte membrane, with formation exocytic microvesicles or microparticles hemolysis, which we hypothesized could impair vascular function contribute to putative lesion banked blood. Methods Results— We now find that human cells banking accumulation...
Nitrite (NO2−) is an intrinsic signaling molecule that reduced to NO during ischemia and limits apoptosis cytotoxicity at reperfusion in the mammalian heart, liver, brain. Although mechanism of nitrite-mediated cytoprotection unknown, a mediator ischemic preconditioning cell-survival program. Analogous temporally distinct acute delayed cytoprotective phenotypes, we report both (24 h before ischemia) exposure physiological concentrations nitrite, given systemically or orally, potently cardiac...
To determine the relative contributions of endothelial-derived nitric oxide (NO) vs. intravascular nitrogen species in regulation human blood flow, we simultaneously measured forearm flow and arterial venous levels plasma nitrite, LMW-SNOs HMW-SNOs, red cell S-nitrosohemoglobin (SNO-Hb). Measurements were made at rest during regional inhibition NO synthesis, followed by exercise. Surprisingly, found significant circulating arterial-venous nitrite gradients, providing a novel delivery source...