A5066702921- Trace Elements in Health
- Nitric Oxide and Endothelin Effects
- Angiogenesis and VEGF in Cancer
- Atherosclerosis and Cardiovascular Diseases
- Cancer, Hypoxia, and Metabolism
- Ferroptosis and cancer prognosis
- Caveolin-1 and cellular processes
- Circular RNAs in diseases
- Nuclear Receptors and Signaling
- Eicosanoids and Hypertension Pharmacology
- MicroRNA in disease regulation
- Cardiovascular Disease and Adiposity
- Biomarkers in Disease Mechanisms
- Metal complexes synthesis and properties
- Extracellular vesicles in disease
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Redox biology and oxidative stress
- Renin-Angiotensin System Studies
- Heavy Metal Exposure and Toxicity
- Alzheimer's disease research and treatments
- Adipose Tissue and Metabolism
- Anesthesia and Neurotoxicity Research
- Cell Adhesion Molecules Research
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Wound Healing and Treatments
Augusta University
2018-2025
Charlie Norwood VA Medical Center
2018-2024
Augusta University Health
2018-2024
Center for Vascular Biology Research
2023-2024
University of Illinois Chicago
2010-2018
Jesse Brown VA Medical Center
2012-2018
University of Arizona
2018
University of Illinois Urbana-Champaign
2012-2015
Illinois College
2015
Showa University
2013
Highlights•PDI functions as a thiol reductase for mitochondrial fission protein Drp1•Loss of PDI induces Drp1 sulfenylation at Cys644, driving endothelial senescence•Dysfunction contributes to impaired wound healing in diabetes•Restoring PDI-Drp1 axis protects against diabetic vascular complicationSummaryMitochondrial dynamics are tightly controlled by fusion and fission, their dysregulation excess reactive oxygen species (ROS) contribute cell (EC) dysfunction. How redox signals regulate...
Abstract Increased aerobic glycolysis in endothelial cells of atheroprone areas blood vessels has been hypothesized to drive increased inflammation and lesion burden but direct links remain be established. Here we show that exposed disturbed flow vivo vitro exhibit levels protein kinase AMP-activated (PRKA)/AMP-activated kinases (AMPKs). Selective deletion Prkaa1 , coding for catalytic subunit alpha1, reduces glycolysis, compromises cell proliferation, accelerates the formation...
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...
Myocardial infarction (MI) is the primary cause of cardiovascular mortality, and therapeutic strategies to prevent or mitigate consequences MI are a high priority. Cardiac progenitor cells (CPCs) have been used treat cardiac injury post-MI, despite poor engraftment, they shown inhibit apoptosis promote angiogenesis through poorly understood paracrine effects. We previously reported that direct injection exosomes derived from CPCs (CPCexo) into mouse hearts provides protection against in...
VEGFR2 (KDR/Flk1) signaling in endothelial cells (ECs) plays a central role angiogenesis. The P-type ATPase transporter ATP7A regulates copper homeostasis, and its angiogenesis is entirely unknown. Here, we describe the unexpected crosstalk between Copper ATP7A, autophagy, degradation. functional significance of this was demonstrated by finding that inducible EC-specific deficient mice or ATP7A-dysfunctional ATP7Amut showed impaired post-ischemic neovascularization. In ECs, loss inhibited...
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....
Exosomes, key mediators of cell-cell communication, derived from type 2 diabetes mellitus (T2DM) exhibit detrimental effects. Exercise improves endothelial function in part via the secretion exosomes into circulation. Extracellular superoxide dismutase (SOD3) is a major secretory copper (Cu) antioxidant enzyme that catalyzes dismutation O2•- to H2 O2 whose activity requires Cu transporter ATP7A. However, role SOD3 exercise-induced angiogenic effects circulating plasma on cells (ECs) T2DM...
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,...
ABSTRACT Endothelial cells (ECs) lining blood vessels sense disturbed flow (D-flow), which drives mitochondrial dysfunction and atherosclerosis. Copper (Cu) is an essential micronutrient, its disruption of homeostasis has been implicated in Cellular Cu levels are tightly controlled by transport proteins including the importer CTR1. Cuproptosis a recently discovered form regulated cell death triggered accumulation, but endogenous stimulants role atherosclerosis remain unknown. Using...
Transient receptor potential melastatin-2 (TRPM2) channel is a nonselective cation that mediates influx of Ca(2+) and Na(+) with relative permeability PCa:PNa ≈0.6 in response to cellular oxidative stress. As angiogenesis ischemic neovascularization are both significantly dependent on oxidant signaling, here we investigated the possible role vascular endothelial growth factor (VEGF)-induced reactive oxygen species production activating TRPM2-dependent signaling mechanism...
Objective: Copper (Cu) is essential micronutrient, and its dysregulation implicated in aortic aneurysm (AA) development. The Cu exporter ATP7A (copper-transporting P-type ATPase/Menkes ATPase) delivers via the chaperone Atox1 (antioxidant 1) to secretory enzymes, such as lysyl oxidase, excludes excess Cu. Lysyl oxidase shown protect against AA formation. However, role mechanism of pathogenesis remain unknown. Approach Results: Here, we show that chelator markedly inhibited Ang II...
Copper transporter ATP7A (copper-transporting/ATPase) is required for full activation of SOD3 (extracellular superoxide dismutase), which secreted from vascular smooth muscle cells (VSMCs) and anchors to endothelial cell surface preserve function by scavenging extracellular superoxide. We reported that protein expression activity are decreased in insulin-deficient type 1 diabetes mellitus vessels, thereby, inducing superoxide-mediated dysfunction, rescued insulin treatment. However, it...
Objective— Vascular smooth muscle cell (VSMC) migration is critically important for neointimal formation after vascular injury and atherosclerosis lesion formation. Copper (Cu) chelator inhibits formation, we previously demonstrated that Cu transport protein antioxidant-1 (Atox1) involved in Cu-induced growth. However, role of Atox1 VSMC unknown. Approach Results— Here, show expression upregulated injured vessel, it colocalized with the transporter ATP7A, one downstream targets Atox1, mainly...
Platelet-derived growth factor (PDGF) stimulates vascular smooth muscle cell (VSMC) migration and neointimal formation in response to injury. We previously identified IQ-domain GTPase-activating protein 1 (IQGAP1) as a novel VEGF receptor 2 binding scaffold involved endothelial migration. However, its role VSMC vivo is unknown. Here we show that PDGF stimulation rapidly promotes IQGAP1 association with receptor-β (PDGFR) well tyrosine phosphorylation cultured VSMC. Overexpression or...
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...
Oxidative stress and endothelial dysfunction contribute to vascular complication in diabetes. Extracellular superoxide dismutase (SOD3) is one of the key antioxidant enzymes that obtains copper via transporter ATP7A. SOD3 secreted from smooth muscles cells (VSMCs) anchors at surface. The role ATP7A type 1 diabetes mellitus (T1DM) entirely unknown. Here we show specific activity SOD3, but not SOD1, decreased, which associated with increased O2•− production aortas streptozotocin-induced...
Inflammation, oxidative stress, and copper (Cu) play an important role in cardiovascular disease, including atherosclerosis. We previously reported that cytosolic Cu chaperone antioxidant-1 (Atox1) translocates to the nucleus response inflammatory cytokines or exogenous Atox1 is localized at endothelium of inflamed atherosclerotic aorta. However, roles nuclear their function are poorly understood. Here we showed deficiency ApoE−/− mice with a Western diet exhibited significant reduction...
Background In endothelial cells (ECs), glycolysis, regulated by PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase, isoform-3), is the major metabolic pathway for ATP generation. preclinical peripheral artery disease models, VEGF
High blood pressure has been shown to elicit impaired dilation in the vasculature. The purpose of this investigation was elucidate mechanisms through which high may vascular dysfunction and determine regular aerobic exercise protects arteries against pressure. Male C57BL/6J mice were subjected 2 wk voluntary running (~6 km/day) for comparison with sedentary controls. Hindlimb adipose resistance dissected from measurements flow-induced (FID; or without intraluminal exposure) protein...