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1.
Osteoarthr Cartil Open ; 5(2): 100354, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36968250

ABSTRACT

Objective: We aimed to delineate a novel soluble Biglycan Neo-epitope-BGN262 in saliva from young reference and osteoarthritic horses in conjunction with the influence of short-term training exercise, riding surface hardness, circadian rhythm, and feeding on its soluble levels. Design: A custom-made inhibition ELISA was used for the quantification of BGN262 in saliva. Cohort 1: A cross-sectional study comprising reference (N â€‹= â€‹19) and OA horses (N â€‹= â€‹9) with radiographically classified subchondral bone sclerosis. Receiver operating characteristic curve analysis was performed to evaluate the robustness of BGN262. Cohorts 2 (N â€‹= â€‹5) & 3 (N â€‹= â€‹7): Longitudinal studies of sampling during a short-term training exercise (sand-fibre) and a cross-over design of short-training exercise on 2 different riding arenas (sand and sand-fibre), respectively. Capillary western immunoassay was used to determine the BGN262 molecular size in a selection of saliva samples collected from cohort 1. Results: Cohort 1: Salivary BGN262 levels were significantly higher in the OA group. The Receiver operating characteristic curve analysis showed an area under the curve of 0.8304 [0.6386 to 1.022], indicating a good separation from the reference group. Cohorts 2 & 3: Salivary BGN262 levels significantly changed during the exercise on sand and sand-fibre arena, with a trend towards higher levels for sand-fibre. The size of the BGN262 fragment determined by Capillary western assay was 18 â€‹kDa. Conclusions: The data presented show saliva BGN262 levels as a novel biomarker in evaluating the influence of exercise, and interaction with riding arenas alongside assessing osteoarthritis severity.

2.
Equine Vet J ; 49(5): 662-667, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28097685

ABSTRACT

BACKGROUND: Clinical tools to diagnose the early changes of osteoarthritis (OA) that occur in the articular cartilage are lacking. OBJECTIVES: We sought to identify and quantify a novel cartilage oligomeric matrix protein (COMP) neoepitope in the synovial fluid from the joints of healthy horses and those with different stages of OA. STUDY DESIGN: In vitro quantitative proteomics and assay development with application in synovial fluids samples obtained from biobanks of well-characterised horses. METHODS: Articular cartilage explants were incubated with or without interleukin-1ß for 25 days. Media were analysed via quantitative proteomics. Synovial fluid was obtained from either normal joints (n = 15) or joints causing lameness (n = 17) or with structural OA lesions (n = 7) and analysed for concentrations of the COMP neoepitope using a custom-developed inhibition enzyme-linked immunosorbent assay (ELISA). Explants were immunostained with polyclonal antibodies against COMP and the COMP neoepitopes. RESULTS: Semitryptic COMP peptides were identified and quantified in cell culture media from cartilage explants. A rabbit polyclonal antibody was raised against the neoepitope of the N-terminal portion of one COMP fragment (sequence SGPTHEGVC). An inhibition ELISA was developed to quantify the COMP neoepitope in synovial fluid. The mean concentration of the COMP neoepitope significantly increased in the synovial fluid from the joints responsible for acute lameness compared with normal joints and the joints of chronically lame horses and in joints with chronic structural OA. Immunolabelling for the COMP neoepitope revealed a pericellular staining in the interleukin-1ß-stimulated explants. MAIN LIMITATIONS: The ELISA is based on polyclonal antisera rather than a monoclonal antibody. CONCLUSIONS: The increase in the COMP neoepitope in the synovial fluid from horses with acute lameness suggests that this neoepitope has the potential to be a unique candidate biomarker for the early molecular changes in articular cartilage associated with OA.


Subject(s)
Cartilage Oligomeric Matrix Protein/cerebrospinal fluid , Horse Diseases/cerebrospinal fluid , Lameness, Animal/cerebrospinal fluid , Osteoarthritis/veterinary , Animals , Biomarkers , Glycoproteins , Horses , Matrilin Proteins , Osteoarthritis/cerebrospinal fluid , Synovial Fluid/metabolism
4.
J Intern Med ; 262(5): 526-36, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17908161

ABSTRACT

OBJECTIVE: We investigated whether levels of C-reactive protein (CRP), interleukin-6 (IL-6), secretory phospholipase A(2) group IIA (sPLA(2)-IIA) and intercellular adhesion molecule-1 (ICAM-I) predict late outcomes in patients with acute coronary syndromes (ACS). DESIGN: Prospective longitudinal study. CRP (mg L(-1)), IL-6 (pg mL(-1)), sPLA(2)-IIA (ng mL(-1)) and ICAM-1 (ng mL(-1)) were measured at days 1 (n = 757) and 4 (n = 533) after hospital admission for ACS. Their relations to mortality and rehospitalization for myocardial infarction (MI) and congestive heart failure (CHF) were determined. SETTING: Coronary Care Unit at Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: Patients with ACS alive at day 30; median follow-up 75 months. RESULTS: Survival was related to day 1 levels of all markers. After adjustment for confounders, CRP, IL-6 and ICAM-1, but not sPLA(2)-IIA, independently predicted mortality and rehospitalization for CHF. For CRP, the hazard ratio (HR) was 1.3 for mortality (95% confidence interval (CI): 1.1-1.5, P = 0.003) and 1.4 for CHF (95% CI: 1.1-1.9, P = 0.006). For IL-6, HR was 1.3 for mortality (95% CI: 1.1-1.6, P < 0.001) and 1.4 for CHF (95% CI: 1.1-1.8, P = 0.02). For ICAM-1, HR was 1.2 for mortality (95% CI: 1.0-1.4, P = 0.04) and 1.3 for CHF (95% CI: 1.0-1.7, P = 0.03). No marker predicted MI. Marker levels on day 4 provided no additional predictive value. CONCLUSIONS: In patients with ACS, CRP, IL-6, sPLA(2)-IIA and ICAM-1 are associated with long-term mortality and CHF, but not reinfarction. CRP, IL-6 and ICAM-1 provide prognostic information beyond that obtained by clinical variables.


Subject(s)
Acute Coronary Syndrome/blood , C-Reactive Protein/analysis , Group II Phospholipases A2/blood , Intercellular Adhesion Molecule-1/blood , Interleukin-6/blood , Aged , Biomarkers/blood , Female , Humans , Longitudinal Studies , Male , Middle Aged , Odds Ratio , Patient Readmission , Prognosis , Prospective Studies , Risk Assessment/methods , Time Factors
5.
J Intern Med ; 262(6): 659-67, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17927738

ABSTRACT

OBJECTIVES: Few studies have investigated the composition of unstable coronary plaques in vivo in humans. The aims of this study were to investigate if substances released from plaques during percutaneous coronary intervention (PCI) under distal protection could give information about plaque composition and also indicate possible biomarkers in plasma that may be used to identify patients at risk. METHODS AND RESULTS: Twenty patients with acute coronary syndromes undergoing PCI with distal protection were included. Plasma samples were taken before, during, and after the PCI in the aortic root, locally in the culprit vessel and intravenously. Plasma was analysed for possible markers of plaque instability. During PCI, local increases were observed for matrix metalloproteinase 9 (MMP-9), protein (P < 0.001) as well as activity (P < 0.001), interleukin 6 (IL-6; P < 0.01) and oxidized low-density lipoprotein (oxLDL; P = 0.01) in the culprit coronary artery. A systemic inflammatory response was also seen with increased levels of IL-10, MMP-3, serum amyloid A and C-reactive protein, but with no increase in MMP-9. CONCLUSIONS: Our study shows that local sampling of blood under distal protection may be used to analyse coronary plaques and to identify biomarkers for unstable plaques. Our results suggest that MMP-9 is a potential biomarker, and that IL-6, MMP9 and possibly oxLDL are released from plaques.


Subject(s)
Acute Coronary Syndrome/therapy , Angioplasty, Balloon, Coronary/methods , Blood Proteins/analysis , Coronary Artery Disease/blood , Coronary Artery Disease/therapy , Matrix Metalloproteinase 9/blood , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/immunology , Adult , Aged , Biomarkers/blood , C-Reactive Protein/analysis , Coronary Artery Disease/immunology , Female , Humans , Interleukin-10/blood , Interleukin-6/blood , Lipoproteins, LDL/blood , Male , Matrix Metalloproteinase 3/blood , Middle Aged , Serum Amyloid A Protein/analysis , Specimen Handling , Statistics, Nonparametric
6.
J Intern Med ; 251(4): 338-47, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11952885

ABSTRACT

OBJECTIVES: To study the effect of statins on plasma markers for inflammation. DESIGN: Patients with hypercholesterolemia were randomized in one of the following treatments: Simvastatin (S) + placebo: S 40 mg for 6 weeks - S 80 mg for 6 weeks - S 80 mg for 24 weeks and Atorvastatin (A) + placebo: A 20 mg for 6 weeks - A 40 mg for 6 weeks - A 80 mg for 24 weeks. SUBJECTS: Forty-seven patients with hypercholesterolemia were recruited in four different outpatient clinics. MAIN OUTCOME MEASURES: Samples were obtained at randomization after 6, 12 and 36 weeks. Plasma or serum was analysed for lipids and for inflammation markers: C-reactive protein (CRP), serum amyloid A (SAA), soluble phospholipase A2 (SPLA2), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6). RESULTS: The reduction in LDL was similar for the two statins, except at the highest dose of atorvastatin (41 vs. 47%). The increase in HDL tended to be more pronounced in the simvastatin group, significantly so on the highest dose of atorvastatin (P < 0.05). CRP and SAA was significantly reduced by atorvastatin, whilst no reduction was seen for simvastatin. There was a significant difference in treatment effects between the two statins. Both statins caused a reduction in SPLA2. For IL-6 and ICAM-1 only small and inconsistent reductions were observed for both statins. CONCLUSION: Atorvastatin reduced the liver-derived acute-phase reactants, CRP and SAA, whilst the effect of simvastatin was small or absent. Small and inconsistent effects were seen for both statins on plasma levels of IL-6 and ICAM-1.


Subject(s)
Anticholesteremic Agents/therapeutic use , Heptanoic Acids/therapeutic use , Hypercholesterolemia/drug therapy , Inflammation/blood , Pyrroles/therapeutic use , Simvastatin/therapeutic use , Adult , Aged , Atorvastatin , Biomarkers/blood , C-Reactive Protein/metabolism , Female , Humans , Intercellular Adhesion Molecule-1/blood , Interleukin-6/blood , Male , Middle Aged
7.
Circulation ; 102(21): 2569-75, 2000 Nov 21.
Article in English | MEDLINE | ID: mdl-11085958

ABSTRACT

BACKGROUND: Human monocyte-derived macrophages synthesize numerous proinflammatory and prothrombotic substances, including lipid mediators, such as platelet-activating factor (PAF), which may play a major role in the onset and perpetuation of atherosclerotic lesions. In addition, both monocytes and macrophages express PAF receptors (PAF-R). The expression of PAF-R is transcriptionally downregulated by oxidized LDL in in vitro primary cultures of monocyte/macrophages. In this study, we evaluated the expression of PAF-R in human carotid plaque tissue, in foam cells isolated from human carotid plaques, and in primary cultures of umbilical smooth muscle cells (SMCs). METHODS AND RESULTS: We show that PAF-R was expressed at low levels in foam cells compared with monocyte/macrophages in plaques, as assessed by immunohistochemical staining and in situ hybridization. In addition, low levels of mRNA were also detected by RT-PCR in isolated human carotid foam cells. A prominent finding of our study was the demonstration that contractile SMCs were positive for PAF-R, and its mRNA was extracted from primary cultures of umbilical SMCs. CONCLUSIONS: As macrophages loose their inflammatory phenotype on transformation into foam cells, they may equally loose their capacity of defense against aggression. We postulate that the diminished expression of PAF-R may be deleterious in the context of plaque formation and progression. The observation that arterial SMCs of contractile phenotype express PAF-R opens new avenues concerning the migration of these cells from media to intima and atherosclerotic plaque formation.


Subject(s)
Arteriosclerosis/metabolism , Carotid Arteries/metabolism , Platelet Membrane Glycoproteins/biosynthesis , Receptors, Cell Surface , Receptors, G-Protein-Coupled , Antigens, Differentiation/metabolism , Arteriosclerosis/pathology , Carotid Arteries/pathology , Cell Nucleus/metabolism , Cell Nucleus/pathology , Cells, Cultured , Cytoplasm/metabolism , Cytoplasm/pathology , Disease Progression , Extracellular Matrix/metabolism , Extracellular Matrix/pathology , Foam Cells/cytology , Foam Cells/metabolism , Humans , Immunohistochemistry , In Situ Hybridization , Macrophages/cytology , Macrophages/metabolism , Monocytes/cytology , Monocytes/metabolism , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/metabolism , Platelet Membrane Glycoproteins/genetics , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction
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