A5026547402- Diabetes, Cardiovascular Risks, and Lipoproteins
- Peroxisome Proliferator-Activated Receptors
- Cholesterol and Lipid Metabolism
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nitric Oxide and Endothelin Effects
- Atherosclerosis and Cardiovascular Diseases
- Lipoproteins and Cardiovascular Health
- Advanced Glycation End Products research
- Diabetes Management and Research
- Paraoxonase enzyme and polymorphisms
- Hormonal Regulation and Hypertension
- Diabetes and associated disorders
- Cancer, Lipids, and Metabolism
- Pancreatitis Pathology and Treatment
- Antioxidant Activity and Oxidative Stress
- Metal-Catalyzed Oxygenation Mechanisms
- Metabolomics and Mass Spectrometry Studies
- Diabetes Treatment and Management
- Redox biology and oxidative stress
- Helicobacter pylori-related gastroenterology studies
- Apelin-related biomedical research
- Extracellular vesicles in disease
- Galectins and Cancer Biology
- Inflammasome and immune disorders
- Advanced Proteomics Techniques and Applications
University of Washington
2015-2025
Institute of Nutrition, Metabolism and Diabetes
2024
Mayo Clinic in Arizona
2016
Mayo Clinic
2016
Cornell University
2014
Florida Atlantic University
2014
University of California, San Francisco
2008
High density lipoprotein (HDL) is the major carrier of lipid hydroperoxides in plasma, but it not yet established whether HDL proteins are damaged by reactive nitrogen species circulation or artery wall. One pathway that generates such involves myeloperoxidase (MPO), a constituent wall macrophages. Another peroxynitrite, potent oxidant generated reaction nitric oxide with superoxide. Both MPO and peroxynitrite produce 3-nitrotyrosine vitro. To investigate involvement atherogenesis, we...
High density lipoprotein (HDL) isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels 3-nitrotyrosine 3-chlorotyrosine. Myeloperoxidase (MPO) is only known source 3-chlorotyrosine in humans, indicating that MPO oxidizes HDL vivo. In current studies, we used tandem mass spectrometry to identify major sites tyrosine oxidation when lipid-free apolipoprotein A-I (apoA-I), protein HDL, was exposed or peroxynitrite...
HDL protects against vascular disease by accepting free cholesterol from macrophage foam cells in the artery wall. This pathway is critically dependent on lecithin:cholesterol acyltransferase (LCAT), which rapidly converts to cholesteryl ester. The physiological activator of LCAT apolipoprotein A-I (apoA-I), major protein. However, removal compromised if apoA-I exposed reactive intermediates. In humans with established cardiovascular disease, myeloperoxidase (MPO) oxidizes HDL, and oxidation...
Rationale: The efflux capacity of high-density lipoprotein (HDL) with cultured macrophages associates strongly and negatively coronary artery disease status, indicating that impaired sterol might be a marker—and perhaps mediator—of atherosclerotic burden. However, the mechanisms contribute to remain poorly understood. Objective: Our aim was determine relationship between myeloperoxidase-mediated oxidative damage apolipoprotein A-I, major HDL protein, ability remove cellular cholesterol by...
HDL from healthy humans and lean mice inhibits palmitate-induced adipocyte inflammation; however, the effect of inflammatory state on functional properties adipocytes is unknown. Here, we found that injected with AgNO3 fails to inhibit inflammation reduces cholesterol efflux 3T3-L1 adipocytes. Moreover, isolated obese moderate systemic lupus erythematosus had similar effects. Since serum amyloid A (SAA) concentrations in increase inflammation, investigated whether elevated SAA a causal...
Dysfunctional high density lipoprotein (HDL) is implicated in the pathogenesis of cardiovascular disease, but underlying pathways remain poorly understood. One potential mechanism involves covalent modification by reactive carbonyls apolipoprotein A-I (apoA-I), major HDL protein. We therefore determined whether resulting from lipid peroxidation (malondialdehyde (MDA) and hydroxynonenal) or carbohydrate oxidation (glycolaldehyde, glyoxal, methylglyoxal) covalently modify lipid-free apoA-I...
Type 1 diabetes mellitus (T1DM) increases the risk of atherosclerotic cardiovascular disease (CVD) in humans by poorly understood mechanisms. Using mouse models T1DM-accelerated atherosclerosis, we found that relative insulin deficiency rather than hyperglycemia elevated levels apolipoprotein C3 (APOC3), an prevents clearance triglyceride-rich lipoproteins (TRLs) and their remnants. We then showed serum APOC3 predict incident CVD events subjects with T1DM Coronary Artery Calcification...
Helicobacter pylori (Hp) infects the stomach of 50% world's population. Importantly, chronic infection by this bacterium correlates with appearance several extra-gastric pathologies, including neurodegenerative diseases. In such conditions, brain astrocytes become reactive and neurotoxic. However, it is still unclear whether highly prevalent or nanosized outer membrane vesicles (OMVs) they produce, can reach brain, thus affecting neurons/astrocytes. Here, we evaluated effects Hp OMVs on...
An imbalance between the proteolytic activity of matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs) is implicated in injury during inflammation. The N-terminal cysteine TIMP-1 plays a key role inhibitory protein because it coordinates essential catalytic Zn2+ MMP, preventing metal ion from functioning. important mechanism for controlling interaction TIMPs with MMPs might involve hypochlorous acid (HOCl), potent oxidant produced by myeloperoxidase (MPO) system phagocytes. Here, we...
Acrolein is a highly reactive α,β-unsaturated aldehyde, but the factors that control its reactions with nucleophilic groups on proteins remain poorly understood. Lipid peroxidation and threonine oxidation by myeloperoxidase are potential sources of acrolein during inflammation. Because both pathways implicated in atherogenesis high density lipoprotein (HDL) anti-atherogenic, we investigated possibility might target major protein HDL, apolipoprotein A-I (apoA-I), for modification. Tandem mass...
High-density lipoprotein (HDL) mediates reverse cholesterol transport (RCT), wherein excess is conveyed from peripheral tissues to the liver and steroidogenic organs. During this process HDL continually transitions between subclass sizes, each with unique biological activities. For instance, RCT initiated by interaction of lipid-free/lipid-poor apolipoprotein A-I (apoA-I) ABCA1, a membrane-associated lipid transporter, form nascent HDL. Because nearly all circulating apoA-I lipid-bound,...
An important event in cholesterol metabolism is the efflux of cellular by apolipoprotein A-I (apoA-I), major protein high density lipoproteins (HDL). Lipid-free apoA-I preferred substrate for ATP-binding cassette A1, which promotes from macrophage foam cells arterial wall. However, vast majority plasma associated with HDL, and mechanisms generation lipid-free remain poorly understood. In current study, we used fluorescently labeled that exhibits a distinct fluorescence emission spectrum when...
Cardiovascular disease is the leading cause of death in end-stage renal (ESRD) patients treated with hemodialysis. An important contributor might be a decline cardioprotective effects high-density lipoprotein (HDL). One factor affecting HDL's properties may involve alterations protein composition HDL. In current study, we used complementary proteomics approaches to detect and quantify relative levels proteins HDL isolated from control ESRD subjects. Shotgun analysis 20 40 subjects identified...
Coronary endothelial dysfunction (ED)-an early marker of atherosclerosis-increases the risk cardiovascular events.We tested hypothesis that cholesterol efflux capacity and high-density lipoprotein (HDL) particle concentration predict coronary ED better than HDL-cholesterol (HDL-C).We studied 80 subjects with nonobstructive (<30% stenosis) artery disease. was defined as <50% change in blood flow response to intracoronary infusions acetylcholine during diagnostic angiography. Cholesterol HDL...
Coenzyme Q10 (CoQ10) supplementation improves mitochondrial coupling of respiration to oxidative phosphorylation, decreases superoxide production in endothelial cells, and may improve functional cardiac capacity patients with congestive heart failure. There are no studies evaluating the safety, tolerability efficacy varying doses CoQ10 chronic hemodialysis patients, a population subject increased stress. We performed dose escalation study test hypothesis that therapy is safe, well-tolerated,...
Individuals with type 1 diabetes (T1D) generally have normal or even higher HDL (high-density lipoprotein)-cholesterol levels than people without yet are at increased risk for atherosclerotic cardiovascular disease (CVD). Human is a complex mixture of particles that can vary in cholesterol content by >2-fold. To investigate if specific subspecies contribute to the atherosclerosis associated T1D, we created mouse models T1D exhibit human-like subspecies. We also measured and their association...