A5031600948- High Altitude and Hypoxia
- Hemoglobinopathies and Related Disorders
- Pulmonary Hypertension Research and Treatments
- Hemoglobin structure and function
- Neuroscience of respiration and sleep
- Iron Metabolism and Disorders
- Heme Oxygenase-1 and Carbon Monoxide
- Cancer, Hypoxia, and Metabolism
- Eicosanoids and Hypertension Pharmacology
- Cardiovascular and Diving-Related Complications
- Heart Rate Variability and Autonomic Control
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Respiratory Support and Mechanisms
- Erythrocyte Function and Pathophysiology
- Cardiovascular and exercise physiology
- Neonatal Health and Biochemistry
- Adipose Tissue and Metabolism
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Traumatic Brain Injury and Neurovascular Disturbances
- Travel-related health issues
- Cardiovascular Function and Risk Factors
- Metabolism and Genetic Disorders
- Nitric Oxide and Endothelin Effects
- Neonatal Respiratory Health Research
- Histone Deacetylase Inhibitors Research
University of Colorado Anschutz Medical Campus
2016-2025
University of Colorado Denver
2016-2025
University of Colorado Hospital
2008-2024
University of Colorado Health
2004-2024
Pediatrics and Genetics
2018
Denver VA Medical Center
2012-2017
University of Kentucky
2017
University Hospital of Zurich
2015
University of Zurich
2015
Imperial College London
2014
Histone deacetylase (HDAC) inhibitors are efficacious in models of hypertension-induced left ventricular heart failure. The consequences HDAC inhibition the context pulmonary hypertension with associated right cardiac remodeling poorly understood.This study was performed to assess utility selective small-molecule class I HDACs a preclinical model hypertension.Rats were exposed hypobaric hypoxia for 3 weeks absence or presence benzamide inhibitor, MGCD0103, which selectively inhibits 1, 2,...
Abstract Pulmonary arterial hypertension (PAH) is an obstructive disease of the precapillary pulmonary arteries. Schistosomiasis-associated PAH shares altered vascular TGF-β signalling with idiopathic, heritable and autoimmune-associated etiologies; moreover, blockade can prevent experimental (PH) in pre-clinical models. regulated at level activation, but how activated this unknown. Here we show activation by thrombospondin-1 (TSP-1) both required sufficient for development PH Schistosoma...
Rationale: Hemolysis occurs not only in conditions such as sickle cell disease and malaria but also during transfusion of stored blood, extracorporeal circulation, sepsis. Cell-free Hb depletes nitric oxide (NO) the vasculature, causing vasoconstriction eventually cardiovascular complications. We hypothesize that Hb-binding proteins may preserve vascular NO signaling hemolysis.Objectives: Characterization an archetypical function by which scavenger could hemolysis.Methods: investigated...
Understanding differences in gene expression that increase risk for pulmonary arterial hypertension (PAH) is essential to understanding the molecular basis disease. Previous studies on patient samples were limited by end-stage disease effects or use of nonadherent cells, which are not ideal model vascular cells vivo. These addressed hypothesis pathological processes associated with PAH may be identified via a genetic signature common across multiple cell types. Expression array experiments...
Lung side population (SP) cells are resident lung precursor with both epithelial and mesenchymal potential that believed to play a role in normal development repair. Neonatal hyperoxic exposure impairs leading long-term decrease gas exchange surfaces. The hypothesis SP altered during impaired has not been studied. To address this issue, we characterized the endothelial of neonatal subsets from mice following room air recovery. were isolated sorted on basis their capacity efflux Hoechst...
Chloride intracellular channel 4 (CLIC4) is highly expressed in the endothelium of remodeled pulmonary vessels and plexiform lesions patients with arterial hypertension. CLIC4 regulates vasculogenesis through endothelial tube formation. Aberrant expression may contribute to vascular pathology hypertension.CLIC4 protein was increased plasma blood-derived cells from idiopathic hypertension 3 rat models gene deletion markedly attenuated development chronic hypoxia-induced mice. Adenoviral...
Cell-free hemoglobin (Hb) exposure may be a pathogenic mediator in the development of pulmonary arterial hypertension (PAH), and when combined with chronic hypoxia potential for exacerbation PAH vascular remodeling is likely more pronounced. We hypothesized that Hb contribute to hypoxia-driven collectively as prooxidant, inflammatory, nitric oxide (NO) scavenger. Using programmable micropump technology, we exposed male Sprague-Dawley rats housed under room air or 12 30 mg per day 3, 5, 7 wk....
Excess superoxide has been implicated in pulmonary hypertension (PH). We previously found lung overexpression of the antioxidant extracellular dismutase (EC-SOD) attenuates PH and artery (PA) remodeling. Although comprising a small fraction total SOD activity most tissues, EC-SOD is abundant arteries. hypothesize that selective loss vascular promotes hypoxia-induced through redox-sensitive signaling pathways. EC-SOD(loxp/loxp) × Tg(cre/SMMHC) mice (SMC KO) received tamoxifen to conditionally...
Optimal right ventricular (RV) function in pulmonary hypertension (PH) requires structural and functional coupling between the RV cardiomyocyte its adjacent capillary network. Prior investigations have indicated that vascular rarefaction occurs PH, which could contribute to failure by reduced delivery of oxygen or other metabolic substrates. However, it has not been determined if results from relative underproliferation setting tissue hypertrophy actual loss vessels. It is also unknown...
Intravascular sickling and lysis of red blood cells, a hallmark feature sickle cell disease (SCD), releases hemoglobin (Hb) into the circulation. Increased cell-free Hb has been linked to vasculopathy in vitro lipid oxidation. Scavenger plasma proteins haptoglobin (Hp) hemopexin (Hpx) can attenuate total heme lipid-oxidative capacity but are depleted SCD. Here, we isolated lipids from BERK-SS mice, guinea pigs (GP) infused with heme-albumin, patients SCD undergoing regular exchange...
The medical records of 25 individuals with sickle cell trait and altitude-associated splenic infarct, reported to two Colorado physicians, were reviewed. Electrospray mass spectroscopy was performed on blood samples from a cohort 10 the rapidly confirm beta hemoglobin phenotype. Only males identified 1.4:1 ratio non-African Americans African Americans, 44% 85% unaware they had trait. Left upper quadrant pain an elevated bilirubin nearly uniformly present. Either abdominal CT or ultrasound...
Abnormalities in Ca2+ homeostasis are associated with cardiac arrhythmias and heart failure. Triadin plays an important role cardiomyocytes. Alternative splicing of a single triadin gene produces multiple isoforms. The cardiac-predominant isoform, mouse MT-1 or human Trisk32, is encoded by exons 1 to 8. In humans, mutations the that lead reduction Trisk32 levels can cause dysfunction arrhythmias. Decreased also common patients However, mechanisms maintain isoform composition remain...
Sickle cell disease and β-Thalassemia are two of the most prevalent hemoglobinopathies worldwide. Both occur due to genetic mutations within HBB gene characterized by red blood dysfunction, anemia, end-organ injury. The spleen liver primary organs where erythrophagocytosis, engulfing cells, occurs in these diseases. Understanding metabolism protein composition tissues can therefore inform extent hemolysis progression. We utilized a multiomics approach highlight metabolomic proteomic...
Key points In low‐oxygen environments, such as high‐altitude, control of blood sugar is disrupted. Further, the activity sympathetic nervous system known to increase when availability oxygen decreased. We have investigated possibility that in partially responsible for disruption control. Using gasbags filled with gas, together a commonly used pressure medication (clonidine) inhibits system, we shown breathing low disrupts control, and this prevented inhibited. This finding has important...
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Dysregulated metabolism characterizes both animal and human forms of pulmonary hypertension (PH). Enzymes involved in fatty acid have previously not been assessed arteries affected by arterial (PAH), how inhibition oxidation (FAO) may attenuate PH remains unclear. Fatty gene transcription was quantified laser-dissected from 10 explanted lungs with advanced PAH (5 idiopathic, 5 associated systemic sclerosis), donors without lung diseases. Effects oxfenicine, a FAO inhibitor, on female Sugen...