A5068788008- Atherosclerosis and Cardiovascular Diseases
- Antioxidant Activity and Oxidative Stress
- Adipokines, Inflammation, and Metabolic Diseases
- Oral microbiology and periodontitis research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Systemic Lupus Erythematosus Research
- Immune Response and Inflammation
- Cholesterol and Lipid Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Lipoproteins and Cardiovascular Health
- Diabetes and associated disorders
- Regulation of Appetite and Obesity
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Inflammasome and immune disorders
- Cell Adhesion Molecules Research
- Cancer, Hypoxia, and Metabolism
- T-cell and B-cell Immunology
- Peroxisome Proliferator-Activated Receptors
- Streptococcal Infections and Treatments
- Galectins and Cancer Biology
- Biochemical Analysis and Sensing Techniques
- Liver Disease Diagnosis and Treatment
- Bariatric Surgery and Outcomes
University of Oulu
2016-2025
Oulu University Hospital
2014-2023
NordLab
2013-2021
University of Pennsylvania
2001-2020
University of Zurich
2020
University of Helsinki
2016
FibroGen (United States)
2016
University of California, San Diego
1998-2008
Biocenter Finland
2006
Public Health Institute
2004
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...
The immune response to oxidized LDL (OxLDL) may play an important role in atherogenesis. Working with apoE-deficient mice, we isolated a panel of OxLDL-specific B-cell lines that secrete IgM Abs specifically bind phospholipids such as 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine (POVPC). These block uptake OxLDL by macrophages, recognize similar oxidation-specific epitopes on apoptotic cells, and are deposited atherosclerotic lesions. were found be structurally functionally...
Many reactive products may be formed when LDL undergoes lipid peroxidation, which in turn can react with lipids, apoproteins, and proteins, generating immunogenic neoepitopes. Autoantibodies recognizing model epitopes of oxidized low density lipoprotein, such as malondialdehydelysine, occur plasma atherosclerotic lesions humans animals. Because apo E-deficient mice develop particularly high titers autoantibodies, we used their spleens to clone 13 monoclonal antibodies various ("E0...
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),...
Experimental studies have suggested that ghrelin plays a role in glucose homeostasis and the regulation of blood pressure (BP). We therefore assessed hypothesis low concentration may be risk factor for type 2 diabetes hypertension. also characterized effect Arg51Gln Leu72Met mutations on concentrations population-based hypertensive (n = 519) control 526) cohorts our OPERA (Oulu Project Elucidating Risk Atherosclerosis) study. The fasting plasma 1,040 subjects were analyzed using...
Apoptosis is recognized as important for normal cellular homeostasis in multicellular organisms. Although there have been great advances our knowledge of the molecular events regulating apoptosis, much less known about receptors on phagocytes responsible apoptotic cell recognition and phagocytosis or ligands cells mediating such recognition. The observations that are under increased oxidative stress oxidized low-density lipoprotein (OxLDL) competes with macrophage binding suggested...
Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of oxidized lipoproteins and apoptotic cells. Adaptive immune responses to various oxidation-specific epitopes play an important role in atherogenesis. However, accumulating evidence suggests that these are also recognized innate receptors, such as scavenger receptors on macrophages, plasma proteins, C-reactive protein (CRP). Here, we provide multiple lines constitute dominant, previously unrecognized target...
The optimal clinical management of patients with antiphospholipid antibody syndrome (APS) is uncertain because a lack an underlying hypothesis to explain why autoantibodies (aPL) form such ubiquitous compounds as phospholipids (PL). In this paper, we demonstrate that many, if not most, aPL are actually directed at neoepitopes oxidized PL, or generated by adduct formation between breakdown products PL and associated proteins. Each cardiolipin (CL) molecule contains four unsaturated fatty...
Abstract —We and others previously showed that immunization of rabbits with different forms oxidized low density lipoprotein (LDL) significantly reduced atherogenesis. We now investigated the effect continued on atherosclerosis in LDL receptor–deficient (LDLR −/− ) mice to determine whether a similar reduction occurred murine models this was due humoral immune responses, ie, formation high titers antibodies oxidation-specific epitopes. Three groups LDLR were repeatedly immunized homologous...
Background— Lipoprotein oxidation plays an important part in atherogenesis. Autoantibodies to oxidation-specific epitopes of LDL occur plasma and atherosclerotic lesions humans animals. The potential role these autoantibodies atherogenesis still remains unsolved. We studied the relationship between different isotypes copper-oxidized malondialdehyde-modified (MDA-LDL) carotid artery intima-media thickness (IMT) a population-based cohort 1022 middle-aged men women. In addition, we relation...
Abstract Objective Cardiovascular disease with premature atherosclerosis is common in patients systemic lupus erythematosus (SLE). We previously identified elevated levels of oxidized low‐density lipoprotein (OxLDL) together autoantibodies related to OxLDL as risk factors for cardiovascular female SLE. Autoantibodies are SLE and cross‐react anticardiolipin antibodies (aCL). therefore hypothesized that lipid peroxidation enhanced general. Methods One hundred forty‐seven 60 age‐ sex‐matched...
Autoantibodies to oxidation-specific epitopes of low density lipoprotein (LDL), such as malondialdehyde-modified LDL (MDA-LDL), occur in plasma and atherosclerotic lesions humans animals. Plasma titers antibodies are correlated with atherosclerosis murine models, several autoantibodies have been cloned. However, human-derived monoclonal oxidized (OxLDL) not yet reported. We constructed a phage display antibody library from patient high anti-MDA-LDL isolated 3 IgG Fab antibodies, which...
The oxidation of low density lipoproteins (LDL) has been correlated with atherogenesis through a variety pathways. process involves nonspecific fragmentation, oxidative breakdown, and modification the lipids protein LDL. yields bioactive products, including aldehyde-containing phospholipids, which can cross-react primary amines (<i>i.e.</i> peptides or phospholipid head groups) to yield Schiff base products. We also demonstrate that such oxidized products may further react post-oxidation...
Obesity is a major public health problem, predisposing subjects to metabolic syndrome, type 2 diabetes, and cardiovascular diseases. Specific prolyl 4-hydroxylases (P4Hs) regulate the stability of hypoxia-inducible factor (HIF), potent governor metabolism, with isoenzyme being main regulator. We investigated whether HIF-P4H-2 inhibition could be used treat obesity its consequences. Hif-p4h-2–deficient mice, fed normal chow or high-fat diet, had less adipose tissue, smaller adipocytes, tissue...
Oxidation-specific epitopes (OSEs) present on apoptotic cells and oxidized low density lipoprotein (OxLDL) represent danger-associated molecular patterns that are recognized by different arcs of innate immunity, including natural IgM antibodies. Here, we investigated whether circulating microparticles (MPs), which small membrane vesicles released or activated cells, physiological carriers OSEs. OSEs MPs isolated from healthy donors patients with ST-segment elevation myocardial infarction...
Disulfide bonds are the most common structural, post-translational modification found in proteins. Antibodies contain up to 25 disulfide depending on type, with scFv fragments containing two disulfides and Fab five or six bonds. The production of antibody that native can be challenging, especially a large scale. protein needs targeted prokaryotic periplasm eukaryotic endoplasmic reticulum. These compartments specialised for bond formation, but both have limitations. Here we show introduction...
There is growing evidence that CD36 has an important physiological function in the uptake of oxidized low density lipoprotein (OxLDL) by macrophages. However, ligand specificity and nature ligands on OxLDL mediate binding to remain ill defined. Results from recent studies suggested some macrophage scavenger receptors involved recognized <i>both</i> lipid protein moieties OxLDL, but there was no conclusive direct for this. The present were undertaken test whether a single, well characterized...
High dietary intakes of tomato products are often associated with a reduced risk CVD, but the atheroprotective mechanisms have not been established. This study was conducted to investigate effects increased intake on plasma lipids and LDL oxidation. The diet intervention included baseline period, 3-week low (no allowed) high (400 ml juice 30 mg ketchup daily). Twenty-one healthy subjects participated in study. Total cholesterol concentration by 5·9 ( sd 10) % P = 0·002) 12·9 17·0) 0·0002)...