A5051208927- Atherosclerosis and Cardiovascular Diseases
- Antioxidant Activity and Oxidative Stress
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Peroxisome Proliferator-Activated Receptors
- Eicosanoids and Hypertension Pharmacology
- Cholesterol and Lipid Metabolism
- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Heme Oxygenase-1 and Carbon Monoxide
- Immune cells in cancer
- Connexins and lens biology
- Immune Response and Inflammation
- Fatty Acid Research and Health
- Phagocytosis and Immune Regulation
- Mitochondrial Function and Pathology
- Immune Cell Function and Interaction
- Liver Disease Diagnosis and Treatment
- Paraoxonase enzyme and polymorphisms
- Cardiovascular Disease and Adiposity
- Inflammasome and immune disorders
- Cancer, Lipids, and Metabolism
- Lipid Membrane Structure and Behavior
- Genomics, phytochemicals, and oxidative stress
- Sphingolipid Metabolism and Signaling
- Advanced Breast Cancer Therapies
University of Virginia
2016-2025
The University of Texas at Austin
2024
Carter Center
2010-2020
Cardiovascular Research Center
2007-2020
University of Virginia Health System
2019
Heinrich Heine University Düsseldorf
2019
Tufts Medical Center
2017
La Trobe University
2017
Biogen (United States)
2016
Bergen Kommune
2012
Entry of monocytes into the vessel wall is an important event in atherogenesis. Previous studies from our laboratory suggest that oxidized arachidonic acid-containing phospholipids present mildly low density lipoproteins (MM-LDL) can activate endothelial cells to bind monocytes. In this study, biologically active were produced by autoxidation 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (Ox-PAPC) and analyzed liquid chromatography electrospray ionization mass spectrometry...
Abstract Atherosclerotic calcification and osteoporosis often coexist in patients, yielding formation of bone mineral vascular walls its simultaneous loss from bone. To assess the potential role lipoproteins both processes, we examined effects minimally oxidized low-density lipoprotein (MM-LDL) several other lipid oxidation products on calcifying cells (CVCs) bone-derived preosteoblasts MC3T3-E1. In CVCs, MM-LDL but not native LDL inhibited proliferation, caused a dose-dependent increase...
We recently cloned monoclonal IgM autoantibodies which bind to epitopes of oxidized low-density lipoprotein (OxLDL) from apoE-deficient mice (EO– autoantibodies). now demonstrate that those EO– were originally selected for binding copper-oxidized lipoproteins (CuOx-LDL), also bound both the protein and lipid moieties CuOx-LDL. The same showed specific products 1-palmitoyl-2-arachidonoyl-phosphatidylcholine (OxPAPC) phospholipid, 1-palmitoyl-2-(5-oxovaleroyl)-phosphatidyl-choline (POVPC),...
Rationale: Macrophages change their phenotype and biological functions depending on the microenvironment. In atherosclerosis, oxidative tissue damage accompanies chronic inflammation; however, macrophage phenotypic changes in response to oxidatively modified molecules are not known. Objective: To examine oxidized phospholipids that present atherosclerotic lesions. Methods Results: We show phospholipid-treated murine macrophages develop into a novel (Mox) is strikingly different from...
Neutrophils promote experimental abdominal aortic aneurysm (AAA) formation via a mechanism that is independent from MMPs (matrix metalloproteinases). Recently, we reported dominant role of IL (interleukin)-1β in the murine AAAs. Here, hypothesis IL-1β-induced neutrophil extracellular trap (NETosis) promotes AAA was tested.
Polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (20:5 (n-3)) inhibit T lymphocyte activation probably by displacing acylated signaling proteins from membrane lipid rafts. Under physiological conditions, saturated acyl residues of partition into the cytoplasmic leaflet with high affinity for rafts that are enriched in acyl-containing lipids. However, biochemical alteration causing displacement PUFA-treated cells is still under debate but could principally be attributed to...
Heme catabolic processes produce the antioxidants biliverdin and bilirubin, as well potent prooxidant free iron. Since these products have opposing effects on oxidative stress, it is not clear whether heme catabolism promotes or inhibits inflammatory processes, including atherosclerotic lesion formation. oxygenase (HO) catalyzes rate-limiting step of catabolism. We used cocultures human aortic endothelial cells smooth muscle to examine possible role HO in early atherosclerosis. oxygenase-1...
Membrane vesicles (MVs) released from activated cells and blebs apoptotic are increased in patients with vascular disease those atherosclerotic lesions, their contribution to inflammatory reactions has been suggested. At sites of inflammation, MVs could serve as rapidly available substrates for peroxidation, carry oxidized compounds activate other cells, amplify inflammation. Here, we show that tert-butyl hydroperoxide-treated endothelial (ECs) blebs, but not Ca(2+) ionophore-treated ECs,...
We previously have demonstrated that oxidized 1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphorylcholine (OxPAPC), a component of minimally modified low density lipoprotein (MM-LDL), activates endothelial cells to bind monocytes. 1-Palmitoyl-2- (5-oxovaleroyl)- (POVPC) and 1- palmitoyl-2-glutaroyl- (PGPC), which are present in OxPAPC, MM-LDL, atherosclerotic lesions, were shown major role the activation cells. now demonstrate these two highly similar molecules dramatically different effects...
Atherosclerosis is a vascular disease characterized by lipid deposition and inflammation within the arterial wall. Oxidized phospholipids (oxPLs), such as 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC) its constituents 1-palmytoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) are concentrated atherosclerotic lesions known to be potent proinflammatory mediators. Phenotypic switching of smooth muscle cells...
Objective— Activation of peroxisome proliferator-activated receptors (PPARs) by lipid-lowering fibrates and insulin-sensitizing thiazolidinediones inhibits vascular inflammation, atherosclerosis, restenosis. Here we investigate if the vasculoprotective anti-inflammatory enzyme heme oxygenase-1 (HO-1) is regulated PPAR ligands in cells. Methods Results— We show that treatment human endothelial smooth muscle cells with leads to expression HO-1. Analysis HO-1 promoter transient transfection...
Abstract —We previously described 3 bioactive oxidation products of 1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphorylcholine (PAPC) containing oxovaleroyl (POVPC), glutaroyl (PGPC), and epoxyisoprostane (PEIPC) groups at the -2 position that were increased in minimally modified/oxidized low density lipoprotein (MM-LDL) rabbit atherosclerotic lesions. We demonstrated specific contrasting effects POVPC PGPC on leukocyte-endothelial interactions an effect PEIPC monocyte binding. The major...
Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation, protects against oxidative stress, and shows potent anti-inflammatory effects. Oxidized phospholipids, which are generated during inflammation apoptosis, modulate inflammatory response by inducing expression of several genes including HO-1. Here we investigated signaling pathways transcriptional events involved induction HO-1 gene oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) human...
Angiogenesis is a common feature observed in advanced atherosclerotic lesions. We hypothesized that oxidized phospholipids (OxPLs), which accumulate vessels can stimulate angiogenesis. found 1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphocholine (OxPAPC) stimulated the formation of sprouts from endothelial cell spheroids and promoted growth capillaries into Matrigel plugs mice. OxPLs expression vascular factor (VEGF) vivo several normal tumor types vitro. In addition, OxPAPC upregulated...
Abstract Inflammatory cell recruitment to local sites of tissue injury and/or infection is controlled by a plethora signalling processes influencing cell-to-cell interactions between the vascular endothelial cells (ECs) in post-capillary venules and circulating leukocytes. Recently, ATP-sensitive P 2 Y purinergic receptors have emerged as downstream regulators EC activation inflammation. However, mechanism(s) regulating cellular ATP release this response remains elusive. Here we report that...