Eva Nozik-Grayck

Eva Nozik-Grayck
University of Colorado | UCD · Section of Critical Care Medicine

MD

About

175
Publications
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3,211
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Publications

Publications (175)
Article
BACKGROUND: H3K27M diffuse midline gliomas (DMGs) are highly aggressive pediatric tumors of pons, thalamus or spinal cord. The only standard-of-care for DMGs is radiation therapy (RT) since the anatomical location of such tumors does not allow surgical resection. Tumor response to RT is at best transient as tumor becomes refractory due to radioresi...
Article
Full-text available
Pulmonary hypertension (PH) represents a group of disorders characterized by elevated mean pulmonary artery (PA) pressure, progressive right ventricular failure, and often death. Some of the hallmarks of pulmonary hypertension include endothelial dysfunction, intimal and medial proliferation, vasoconstriction, inflammatory infiltration, and in situ...
Article
Acute respiratory distress syndrome (ARDS) is a highly morbid pulmonary disease characterized by hypoxic respiratory failure. Its pathogenesis is characterized by unrestrained oxidative stress and inflammation, with long-term sequelae of pulmonary fibrosis and diminished lung function. Unfortunately, prior therapeutic ARDS trials have failed and th...
Article
ROCK, one of the downstream regulators of Rho, controls actomyosin cytoskeleton organization, stress fiber formation, smooth muscle contraction, and cell migration. ROCK plays an important role in the pathologies of cerebral and coronary vasospasm, hypertension, cancer, and arteriosclerosis. Pharmacological-induced systemic inhibition of ROCK affec...
Article
Full-text available
Acute respiratory distress syndrome (ARDS) is a devastating pulmonary disease with significant in-hospital mortality and is the leading cause of death in COVID-19 patients. Excessive leukocyte recruitment, unregulated inflammation, and resultant fibrosis contribute to poor ARDS outcomes. Nanoparticle technology with cerium oxide nanoparticles (CNP)...
Article
Poor maternal diet increases the risk of obesity and type 2 diabetes in offspring, adding to the ever-increasing prevalence of these diseases. In contrast, we find that maternal exercise improves the metabolic health of offspring, and here, we demonstrate that this occurs through a vitamin D receptor-mediated increase in placental superoxide dismut...
Article
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Maternal selenium (Se) deficiency is associated with decreased neonatal Se levels, which increases the risk for neonatal morbidities. There is a hierarchy to selenoprotein expression after Se deficiency in adult rodents, depending on the particular protein and organ evaluated. However, it is unknown how limited Se supply during pregnancy impacts ne...
Article
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Cancers reprogram their metabolism to adapt to environmental changes. In this study, we examined the consequences of altered expression of the mitochondrial enzyme carnitine palmitoyl transferase I (CPT1A) in prostate cancer (PCa) cell models. Using transcriptomic and metabolomic analyses, we compared LNCaP-C4-2 cell lines with depleted (knockdown...
Article
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Background: Selenium (Se) levels decrease in the circulation during acute inflammatory states and sepsis, and are inversely associated with morbidity and mortality. A more specific understanding of where selenoproteins and Se processing are compromised during insult is needed. We investigated the acute signaling response in selenoenzymes and Se pr...
Article
Currently used animal and cellular models for pulmonary arterial hypertension (PAH) only partially recapitulate its pathophysiology in humans and are thus inadequate in reproducing the hallmarks of the disease, inconsistent in portraying the sex-disparity, and unyielding to combinatorial study designs. Here we sought to deploy the ingenuity of micr...
Preprint
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Acute respiratory distress syndrome (ARDS) is a devastating pulmonary disease with significant inhospital mortality and is the leading cause of death in COVID-19 patients. Potential therapies remain limited despite advancements in understanding ARDS pathophysiology. Excessive leukocyte recruitment, unregulated inflammation, and resultant fibrosis c...
Article
Full-text available
Diabetes mellitus affects 451 million people worldwide, and people with diabetes are 3-5 times more likely to develop cardiovascular disease. In vascular tissue, mitochondrial function is important for vasoreactivity. Diabetes-mediated generation of excess reactive oxygen species (ROS) may contribute to vascular dysfunction via damage to mitochondr...
Article
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Objectives Oxidative stress is central to the etiology of many diseases of prematurity. Lower antioxidant defenses render premature infants vulnerable to oxidative damage secondary to infection and oxygen therapy. Antioxidant enzymes (AOE) increase perinatally in the blood and lungs. Many AOE require a micronutrient such as selenium (Se) or zinc (Z...
Article
Oxidative stress is a key contributor to the development of dysregulated inflammation in acute lung injury (ALI). A naturally occurring single nucleotide polymorphism in the key extracellular antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), results in an arginine to glycine substitution (R213G) which promotes resolution of inflammat...
Article
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The HIV-infected population is at a dramatically increased risk of developing pulmonary arterial hypertension (PAH), a devastating and fatal cardiopulmonary disease that is rare amongst the general population. It is increasingly apparent that PAH is a disease with complex and heterogeneous cellular and molecular pathologies, and options for therape...
Article
Fibrotic disorders account for over one third of mortalities worldwide. Despite great efforts to study the cellular and molecular processes underlying fibrosis, there are currently few effective therapies. Dual-stage polymerization reactions are an innovative tool for recreating heterogeneous increases in extracellular matrix (ECM) modulus that are...
Article
Full-text available
Serotonin (5-HT) contributes to the pathogenesis of experimental neonatal pulmonary hypertension (PH) associated with bronchopulmonary dysplasia (BPD). Platelets are the primary source of circulating 5-HT and is released upon platelet activation. Platelet transfusions are associated with neonatal mortality and increased rates of BPD. As BPD is ofte...
Article
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Chronic hypoxia leads to pathologic remodeling of the pulmonary vasculature and pulmonary hypertension (PH). The antioxidant enzyme extracellular superoxide dismutase (SOD3) protects against hypoxia-induced PH. Hyaluronan (HA), a ubiquitous glycosaminoglycan of the lung extracellular matrix, is rapidly recycled at sites of vessel injury and repair....
Article
Full-text available
Clinical studies have demonstrated a strong association between both acute toxic exposure and the repetitive, chronic exposure to acetaminophen (APAP) with pulmonary dysfunction. However, the mechanisms underlying this association are unknown. Preclinical reports have demonstrated that significant bronchiolar injury occurs with toxic APAP exposure,...
Article
A human single nucleotide polymorphism (SNP) in the matrix-binding domain of extracellular superoxide dismutase (EC-SOD), with arginine to glycine substitution at position 213 (R213G), redistributes EC-SOD from the matrix into extracellular fluids. We reported that, following bleomycin (bleo), knockin mice harboring the human R213G SNP (R213G mice)...
Article
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Circulating macrophages recruited to the lung contribute to pulmonary vascular remodeling in various forms of pulmonary hypertension (PH). In this study we investigated a macrophage phenotype characterized by intracellular iron accumulation and expression of antioxidant (HO-1), vasoactive (ET-1), and proinflammatory (IL-6) mediators observed in the...
Article
Full-text available
Key Points Aging-associated inflammation by TNF-α plays an important role in the development of platelet hyperreactivity during aging. Aging-associated platelet hyperreactivity is associated with megakaryocytic inflammatory, metabolic, and mitochondrial reprogramming.
Article
Oxidative stress is well recognized to contribute to the pathogenesis of diverse diseases, including the devastating disease of the lung's blood vessels, pulmonary arterial hypertension (PAH), however, antioxidant-based therapies have been overall disappointing. With the evolution of the field of redox biology, it is now becoming clear that redox r...
Article
Here we sought to elucidate the role of CAR (a cyclic peptide) in the accumulation and distribution of fasudil, a drug for pulmonary arterial hypertension (PAH), in rat lungs and in producing pulmonary specific vasodilation in PAH rats. As such, we prepared liposomes of fasudil and CAR-conjugated liposomal fasudil, assessed the liposomes for CAR co...
Article
Chronic HIV infection in the era of anti-retroviral therapy is associated with dramatically increased risk of developing severe cardio pulmonary disease. Common to these diseases is increased oxidative burden and chronic inflammation despite low viremia and restoration of CD4+ T-cell levels. Soluble viral factors are heavily implicated in these dis...
Article
Diabetes mellitus affects 451 million people worldwide, and people with diabetes are 3-5 times more likely to develop cardiovascular disease. In vascular tissue, mitochondrial function is important for vasodilation and arterial stiffness, both of which are abnormal in diabetes. Diabetes-mediated generation of excess reactive oxygen species (ROS) ma...
Article
Full-text available
The accurate and specific detection of reactive oxygen species (ROS) in different cellular and tissue compartments is essential to the study of redox-regulated signaling in biological settings. Electron paramagnetic resonance spectroscopy (EPR) is the only direct method to assess free radicals unambiguously. Its advantage is that it detects physiol...
Article
Significance: Pulmonary hypertension (PH) is a progressive disease characterized by pulmonary vascular remodeling and lung vasculopathy. The disease displays progressive dyspnea, pulmonary artery uncoupling and right ventricular (RV) dysfunction. The overall survival rate is ranging from 28-72%. Recent Advances: The molecular events that promote t...
Article
Ephrin type-A receptor 2 (EphA2) is a transmembrane receptor which is upregulated in injured lungs, including those treated with bleomycin. YSA peptide (YSAYPDSVPMMS), a mimic of ephrin ligands, binds to EphA2 receptors on cell surface with high affinity. In this study, we assessed the ability of YSA-functionalized and non-functionalized poly (dl-l...
Article
Currently, dual or triple drug combinations comprising different vasodilators are the mainstay for the treatment of pulmonary arterial hypertension (PAH). But the patient outcome continues to be disappointing because the existing combination therapy cannot restrain progression of the disease. Previously, we have shown that when given as a monothera...
Article
Bleomycin is a commonly used cancer therapeutic that is associated with oxidative stress leading to pulmonary toxicity. Bleomycin has been used in animal studies to model pulmonary fibrosis, acute respiratory distress syndrome, and pulmonary hypertension secondary to interstitial lung disease. The toxicity with bleomycin is initiated by direct oxid...
Article
MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression in many diseases, though the contribution of miRNAs to the pathophysiology of lung injury remains obscure. We hypothesized that dysregulation of miRNA expression drives the changes in key genes implicated in the development of lung injury. To test our hypothesis, we utilized a mod...
Article
Extracellular Superoxide Dismutase (EC-SOD), one of three mammalian SOD isoforms, is the sole extracellular enzymatic defense against superoxide. A known human SNP in the matrix-binding domain of EC-SOD characterized by an arginine to glycine substitution at position 213 (R213G), redistributes EC-SOD from the matrix into extracellular fluids. We pr...
Article
Full-text available
Background: Several inflammatory lung diseases display abundant presence of hyaluronic acid (HA) bound to heavy chains (HC) of serum protein inter-alpha-inhibitor (IαI) in the extracellular matrix. The HC-HA modification is critical to neutrophil sequestration in liver sinusoids and to survival during experimental lipopolysaccharide (LPS)-induced...
Conference Paper
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Rationale: Dysregulated hyaluronan (HA) turnover is a newly recognized feature in multiple subgroups of pulmonary hypertension, including PH owing to chronic hypoxia. Extracellular superoxide dismutase (SOD3) protects against hypoxic PH. We hypothesized that hypoxia and vascular SOD3 availability determine the structure of pulmonary HA through regu...
Poster
Full-text available
Rationale: Hyaluronic acid (HA) is released into the extracellular fluid in human sepsis and acute respiratory distress syndrome. Higher concentrations of free HA in the circulation and alveolar fluid predict increased mortality in these conditions. We studied the kinetics of HA release and clearance in the plasma and alveolar compartments in three...
Article
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In infants intolerant of enteral feeding because of intestinal disease, parenteral nutrition may be associated with cholestasis, which can progress to end-stage liver disease. Here we show the function of hepatic macrophages and phytosterols in parenteral nutrition-associated cholestasis (PNAC) pathogenesis using a mouse model that recapitulates th...
Article
Peroxisome-proliferator-activated-receptor-gamma (PPAR-γ) is implicated, in some capacity, in the pathogenesis of pulmonary arterial hypertension (PAH). Rosiglitazone, an oral antidiabetic and PPAR-γ agonist, has the potential to dilate pulmonary arteries and to attenuate arterial remodeling in PAH. Here, we sought to test the hypothesis that rosig...
Article
The lung epithelial glycocalyx is a carbohydrate-enriched layer lining the pulmonary epithelial surface. Although epithelial glycocalyx visualization has been reported, its composition and function remain unknown. Using immunofluorescence and mass spectrometry we identified heparan sulfate (HS) and chondroitin sulfate (CS) within the lung epithelia...
Article
Full-text available
Background: A naturally occurring single nucleotide polymorphism (SNP), (R213G), in extracellular superoxide dismutase (SOD3), decreases SOD3 matrix binding affinity. Humans and mature mice expressing the R213G SNP exhibit increased cardiovascular disease but decreased lung disease. The impact of this SNP on the neonatal lung at baseline or with i...
Article
Pulmonary hypertension (PH) complicating bronchopulmonary dysplasia (BPD) worsens clinical outcomes in former preterm infants. Increased serotonin (5-hydroxytryptamine, 5-HT) signaling plays a prominent role in PH pathogenesis and progression in adults. We hypothesized that increased 5-HT signaling contributes to the pathogenesis of neonatal PH com...
Article
A naturally occurring single nucleotide polymorphism (SNP) (R213G) in extracellular superoxide dismutase (SOD3), a key lung and vascular antioxidant enzyme, decreases tissue binding and increases SOD3 in epithelial lining fluid and plasma. Mice harboring the R213G SNP are protected against bleomycin-induced alveolar inflammation and fibrosis. We hy...
Chapter
When evaluating the role of redox-regulating signaling in pulmonary vascular diseases, it is intriguing to consider the modulation of key antioxidant enzymes like superoxide dismutase (SOD) because SOD isoforms are regulated by redox reactions, and, in turn, modulate downstream redox sensitive processes. The emerging field of redox biology is built...
Presentation
Full-text available
Background and synoptic overview of current work concerning the the role of extracellular superoxide dismutase in regulating hyaluronan turnover during hypoxia