A5032012153- Nitric Oxide and Endothelin Effects
- Amino Acid Enzymes and Metabolism
- Complement system in diseases
- Trace Elements in Health
- Atherosclerosis and Cardiovascular Diseases
- Wound Healing and Treatments
- Adenosine and Purinergic Signaling
- Hormonal Regulation and Hypertension
- Angiogenesis and VEGF in Cancer
- Metabolism and Genetic Disorders
- Renal and related cancers
- Fetal and Pediatric Neurological Disorders
- Chronic Kidney Disease and Diabetes
- Protein Tyrosine Phosphatases
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Adipose Tissue and Metabolism
- Renin-Angiotensin System Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Renal Diseases and Glomerulopathies
- Heavy Metal Exposure and Toxicity
- Metal complexes synthesis and properties
- Pregnancy and preeclampsia studies
- Birth, Development, and Health
- Cerebrospinal fluid and hydrocephalus
- Eicosanoids and Hypertension Pharmacology
Sorbonne Université
2024
Assistance Publique – Hôpitaux de Paris
2024
Hôpital Tenon
2024
Alexion Pharmaceuticals (United States)
2020-2022
AstraZeneca (United States)
2022
University of Illinois Chicago
2010-2016
Argonne National Laboratory
2010-2012
Jesse Brown VA Medical Center
2012
University of Florida
2004-2011
Cardiovascular Research Center
2011
Abstract Copper (Cu), an essential micronutrient, plays a fundamental role in inflammation and angiogenesis; however, its precise mechanism remains undefined. Here we uncover novel of Cu transport protein Antioxidant-1 (Atox1), which is originally appreciated as chaperone recently discovered Cu-dependent transcription factor, inflammatory neovascularization. Atox1 expression upregulated patients mice with critical limb ischemia. Atox1-deficient show impaired perfusion recovery reduced...
Rationale: Copper, an essential nutrient, has been implicated in vascular remodeling and atherosclerosis with unknown mechanism. Bioavailability of intracellular copper is regulated not only by the importer CTR1 (copper transporter 1) but also exporter ATP7A (Menkes ATPase), whose function achieved through copper-dependent translocation from trans -Golgi network (TGN). Platelet-derived growth factor (PDGF) promotes smooth muscle cell (VSMC) migration, a key component neointimal formation....
Abstract Copper (Cu), an essential nutrient, promotes wound healing, however, target of Cu action and underlying mechanisms remain elusive. chaperone Antioxidant-1 (Atox1) in the cytosol supplies to secretory enzymes such as lysyl oxidase (LOX), while Atox1 nucleus functions a Cu-dependent transcription factor. Using mouse cutaneous healing model, here we show that content (by X-ray Fluorescence Microscopy) nuclear are increased after wounding, with without treatment is impaired −/− mice....
p66Shc, a longevity adaptor protein, is demonstrated as key regulator of reactive oxygen species (ROS) metabolism involved in aging and cardiovascular diseases. Vascular endothelial growth factor (VEGF) stimulates cell (EC) migration proliferation primarily through the VEGF receptor-2 (VEGFR2). We have shown that ROS derived from Rac1-dependent NADPH oxidase are VEGFR2 autophosphorylation angiogenic-related responses ECs. However, role p66Shc signaling physiological ECs unknown. Here we show...
Extracellular superoxide dismutase (SOD3) is a secretory copper enzyme involved in protecting angiotensin II (Ang II)-induced hypertension. We found previously that Ang upregulates SOD3 expression and activity as counterregulatory mechanism; however, underlying mechanisms are unclear. Antioxidant 1 (Atox1) shown to act copper-dependent transcription factor, well chaperone, for vitro, but its role II-induced hypertension vivo unknown. Here we show infusion increases Atox1 expression,...
Background Reactive oxygen species (ROS) play an important role in angiogenesis endothelial cells (ECs) vitro and neovascularization vivo. However, little is known about the of endogenous vascular hydrogen peroxide (H2O2) postnatal neovascularization. Methodology/Principal Findings We used Tie2-driven specific catalase transgenic mice (Cat-Tg mice) hindlimb ischemia model to address H2O2 ECs post-ischemic Here we show that Cat-Tg exhibit significant reduction intracellular ECs, blood flow...
Ravulizumab and eculizumab are approved terminal complement inhibitor treatments for atypical hemolytic uremic syndrome (aHUS). was engineered from to have an increased half-life allowing reduced dosing frequency (8-weekly vs. 2-weekly). To account differences in respective clinical trials, a validated balancing technique used enable indirect comparison of ravulizumab treatment efficacy aHUS. Patient-level data four trials were available pooling with two trials. In the primary analysis,...
Cold temperatures have adverse effects on the human cardiovascular system. Endothelin (ET)-1 is a potent vasoconstrictor. We hypothesized that cold exposure increases ET-1 production and upregulates ET type A (ETA) receptors. The aim of this study was to determine effect regulation Four groups rats (6-7 rats/group) were used: three exposed moderate (6.7 +/- 2 degrees C) for 1, 3, 5 wk, respectively, remaining group maintained at room temperature (25 served as control. significantly increased...
The kidney is a major site of arginine synthesis where citrulline converted to via argininosuccinate synthase (ASS) and lyase (ASL). rate-limiting step in by the normal rate delivery uptake renal cortex. We tested whether with chronic disease (CKD) may be compromised. Using 5/6 ablation/infarction (A/I) injury model, we measured as well release at early, moderate, severe stages CKD vs. healthy controls. plasma flow (RPF) arterial-renal venous difference was baseline during infusion....
This study compared the aggregate duration of treatment administration approved eculizumab and ravulizumab regimens resultant productivity implications for patients with atypical hemolytic uremic syndrome (aHUS) their caregivers.The (which includes waiting time medication preparation infusion, recovery, travel to from clinic) was determined a hypothetical population aHUS treated (10 mg/mL) or 100 mg/mL), in clinic at home, 1 year, Germany, Italy, UK, US. The data US used extend previously...
Background.The Fisher 344 (F344) rat kidney transplanted to a Lewis recipient is common model of chronic renal allograft nephropathy (CAN); however, CAN does not develop when the grafted into F344 recipient.In this study we investigated whether difference in nephron number/glomerular volume exists between strains that could contribute greater susceptibility development disease F344.Methods.Separate animals, male and rats, were subjected either sham surgery or right uninephrectomy infarction...
Fetal baroreflex responsiveness increases in late gestation. An important modulator of activity is the generation nitric oxide brainstem nuclei that integrate afferent and efferent reflex activity. The present study was designed to test hypothesis synthase (NOS) isoforms are expressed fetal expression one or more these enzymes reduced Brainstem tissue rapidly collected from sheep known gestational ages (80, 100, 120, 130, 145 days gestation 1 day wk postnatal). Neuronal (nNOS), inducible...
<i>Background/Aims:</i> Reduced renal <i>L</i>-arginine (<i>L</i>-Arg) synthesis/transport, induction of arginases and increased endogenous NOS inhibitor, asymmetric dimethylarginine (ADMA) will inhibit NO production. This study investigated pathways <i>L</i>-Arg synthesis/uptake/utilization, ADMA degradation oxidant/antioxidants in puromycin aminonucleoside (PAN) chronic kidney disease (CKD). <i>Methods:</i> Rats were given low-...
The fawn-hooded hypertensive (FHH) rat develops spontaneous glomerulosclerosis that is ameliorated by inhibition of the angiotensin II type 1 receptor (AT-1). Since kidney damage associated with nitric oxide (NO) deficiency, we investigated how AT-1 antagonism influenced synthase (NOS), as well NOS substrate [L-arginine (L-Arg)] and inhibitor [asymmetric dimethylarginine (ADMA)]. L-Arg synthesized renal argininosuccinate synthase/argininosuccinate lyase (ASS/ASL) then either consumed within...
Atypical hemolytic uremic syndrome is a rare disease caused by complement dysregulation that can lead to progressive kidney damage or death if untreated. Owing its rarity, the impact of atypical and available therapies (eculizumab ravulizumab) on patients' health-related quality life difficult describe, but such data are required for an economic evaluation.The objective this study was estimate utility values syndrome-related attributes in five countries evaluation.Using discrete choice...
Background: Wound healing is important repair process after injury associated with inflammation and angiogenesis. Copper (Cu) plays an role in wound angiogenesis; however, underlying mechanism unknown. Bioavailability of Cu tightly controlled by transport proteins (Cu importer CTR1 exporter ATP7A) chaperone (antioxidant-1, Atox1) which transfers to ATP7A. We reported that Atox1 also functions as a Cu-dependent transcription factor; its unclear. Results: Using mouse skin puncture model, here...
Abstract Background and Aims Malignant hypertension (MHT) is characterized by diffuse microvascular damage caused severe hypertension, often presenting with multiple organ involvement. Cerebrovascular injury, occurring in both acute chronic forms, stands as a hallmark of the disease, being identified up to half patients. Thrombotic microangiopathy (TMA), defined association mechanical hemolytic anemia thrombocytopenia, also emerges frequent complication MHT However, potential contribution...
Copper (Cu) facilitates wound healing and angiogenesis with unknown mechanism. Bioavailability of Cu is controlled by transport-proteins, including cytosolic Cu-chaperone Atox1, which required for activation secretory enzymes. Atox1 also functions as a Cu-dependent transcription factor, but its role in unknown. Using mouse skin puncture model, here we show that protein (8-fold) Cu-level (by X-ray Fluorescence Microscopy; 2.5-fold) were increased wounding tissue wild type (WT) mice at day 7...
The kidney is one of the most complicated organs to transfect due heterogeneity its structure, cellular makeup, and high rate blood flow, reducing “dwell‐time”. We investigated methods LV delivery establish optimal routes allowing greatest localized expression. SD rats were injected with 1x107TU expressing GFP, delivered by: 1) Jugular vein injection (6ml in 10 sec; hydrodynamic delivery) 2) carotid (0.5ml); 3) Intraparenchymal (IPC) (30–200ul) (border inner outer medulla) normal renal flow...
Tumor necrosis factor-TNFα plays a key role in atherosclerosis via NADPH oxidase-derived reactive oxygen species (ROS) and its downstream redox-sensitive inflammatory responses. Copper (Cu) has been implicated inflammation with unknown mechanism. Bioavailability of Cu is controlled by transport-proteins including Cu-chaperone Atox1 which obtains Cu-importer CTR1 localized at plasma membrane. We recently found that also functions as Cu-dependent transcription factor for oxidase p47phox....
A severely chronically protein and calorie restricted young woman with argininosuccinate lyase deficiency developed transient refeeding syndrome (RFS) hyperammonemia after modest diet liberalization following initiation of glycerol phenylbutyrate (GPB). The patient required IV supportive care supplementation potassium, magnesium calcium. She is now doing well on GPB an appropriate maintenance diet. Susceptibility to RFS should be considered in nutritionally patients metabolic disorders