14 results found
Khamis RY, Woollard KJ, Hyde GD, et al., 2016, Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis, Scientific Reports, Vol: 6, ISSN: 2045-2322
We aimed to develop a quantitative antibody-based near infrared fluorescence (NIRF) approachfor the imaging of oxidized LDL in atherosclerosis. LO1, a well- characterized monoclonalautoantibody that reacts with malondialdehyde-conjugated LDL, was labeled with a NIRF dye toyield LO1-750. LO1-750 specifically identified necrotic core in ex vivo human coronary lesions.Injection of LO1-750 into high fat (HF) fed atherosclerotic Ldlr-/-mice led to specific focallocalization within the aortic arch and its branches, as detected by fluorescence moleculartomography (FMT) combined with micro-computed tomography (CT). Ex vivo confocalmicroscopy confirmed LO1-750 subendothelial localization of LO1-750 at sites ofatherosclerosis, in the vicinity of macrophages. When compared with a NIRF reporter of MMPactivity (MMPSense-645-FAST), both probes produced statistically significant increases inNIRF signal in the Ldlr-/- model in relation to duration of HF diet. When withdrawing the HFdiet, the reduction in oxLDL accumulation, as demonstrated with LO1-750, was less markedthan the effect seen on MMP activity. In the rabbit, in vivo injected LO1-750 localization wassuccessfully imaged ex vivo in aortic lesions with a customised intra-arterial NIRF detectioncatheter. A partially humanized chimeric LO1-Fab-Cys localized similarly to the parentantibody in murine atheroma showing promise for future translation.
Iqbal MB, Johns M, Cao J, et al., 2014, PARP-14 combines with tristetraprolin in the selective posttranscriptional control of macrophage tissue factor expression, Blood, Vol: 124, Pages: 3646-3655, ISSN: 0006-4971
Tissue factor (TF) (CD142) is a 47 kDa transmembrane cell surface glycoprotein that triggers the extrinsic coagulation cascade and links thrombosis with inflammation. Although macrophage TF expression is known to be regulated at the RNA level, very little is known about the mechanisms involved. Poly(adenosine 5′-diphosphate [ADP]-ribose)-polymerase (PARP)-14 belongs to a family of intracellular proteins that generate ADP-ribose posttranslational adducts. Functional screening of PARP-14–deficient macrophages mice revealed that PARP-14 deficiency leads to increased TF expression and functional activity in macrophages after challenge with bacterial lipopolysaccharide. This was related to an increase in TF messenger RNA (mRNA) stability. Ribonucleoprotein complex immunoprecipitation and biotinylated RNA pull-down assays demonstrated that PARP-14 forms a complex with the mRNA-destabilizing protein tristetraprolin (TTP) and a conserved adenylate-uridylate-rich element in the TF mRNA 3′ untranslated region. TF mRNA regulation by PARP-14 was selective, as tumor necrosis factor (TNF)α mRNA, which is also regulated by TTP, was not altered in PARP-14 deficient macrophages. Consistent with the in vitro data, TF expression and TF activity, but not TNFα expression, were increased in Parp14−/− mice in vivo. Our study provides a novel mechanism for the posttranscriptional regulation of TF expression, indicating that this is selectively regulated by PARP-14.
Khamis R, Woollard K, Kojima C, et al., 2014, A novel immunoglobulin G autoantibody against a cryptic epitope in low density lipoprotein (LDL) revealed in atherosclerosis
Hyde GD, Taylor RF, Ashton N, et al., 2014, Axl Tyrosine Kinase Protects against Tubulo-Interstitial Apoptosis and Progression of Renal Failure in a Murine Model of Chronic Kidney Disease and Hyperphosphataemia, PLOS ONE, Vol: 9, ISSN: 1932-6203
Khamis RY, Woollard KJ, Hyde GD, et al., 2014, DEVELOPMENT OF WHOLE BODY AND INTRAVASCULAR NEAR-INFRARED OPTICAL MOLECULAR IMAGING OF MARKERS OF PLAQUE VULNERABLITY IN ATHEROSCLEROSIS, Annual Conference of the British-Cardiovascular-Society
Khamis R, Woollard K, Boyle J, et al., 2014, A NOVEL IMMUNOGLOBULIN G AUTOANTIBODY AGAINST LOW DENSITY LIPOPROTEIN (LDL) WITH PATHOGENIC FUNCTIONS, Annual Conference of the British-Cardiovascular-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A121-A121, ISSN: 1355-6037
Iqbal MB, Johns M, Yu SC, et al., 2013, Poly(ADP-ribose) polymerase-14 interacts with tristetraprolin to selectively regulate tissue factor mRNA stability: a novel role for ADP-ribosylation in regulating mRNA turnover and thrombosis, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 178-179, ISSN: 0195-668X
Iqbal MB, Johns M, Yu S-C, et al., 2013, POLY(ADP-RIBOSE) POLYMERASE-14 INTERACTS WITH TRISTETRAPROLIN TO SELECTIVELY REGULATE TISSUE FACTOR MRNA STABILITY: A NOVEL ROLE FOR ADP-RIBOSYLATION IN REGULATING MRNA TURNOVER AND THROMBOSIS, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, Pages: A113-A113, ISSN: 1355-6037
Hyde GD, Gilmore AP, Canfield AE, 2011, GAS6/AXL SIGNALLING SUPRESSES BOTH OSTEOGENIC DIFFERENTIATION AND APOPTOSIS OF VASCULAR SMOOTH MUSCLE CELLS DURING PHOSPHATE-INDUCED MINERALISATION
Ponnusamy A, Sinha S, Hyde GD, et al., 2011, FTI-277 INHIBITS VASCULAR CALCIFICATION BY ACTIVATING DOWNSTREAM PI3K/AKT SIGNALLING AND PREVENTING APOPTOSIS OF VASCULAR SMOOTH MUSCLE CELLS
Hyde GD, Boot-Handford RP, Wallis GA, 2009, Col2a1 lineage tracing reveals that the meniscus of the knee joint develops from a combination of cells with different origins, Annual General Meeting of the British-Society-for-Matrix-Biology, Publisher: WILEY-BLACKWELL PUBLISHING, INC, Pages: A94-A94, ISSN: 0959-9673
Hyde G, Boot-Handford RP, Wallis GA, 2008, Col2a1 lineage tracing reveals that the meniscus of the knee joint has a complex cellular origin, JOURNAL OF ANATOMY, Vol: 213, Pages: 531-538, ISSN: 0021-8782
Hyde G, Dover S, Aszodi A, et al., 2007, Lineage tracing using matrilin-1 gene expression reveals that articular chondrocytes exist as the joint interzone forms, DEVELOPMENTAL BIOLOGY, Vol: 304, Pages: 825-833, ISSN: 0012-1606
Dover SL, Hyde G, Aszodi A, et al., 2006, Determining the origin of articular chondrocytes by lineage tracing, Autumn Meeting of the British-Society-for-Matrix-Biology, Publisher: WILEY-BLACKWELL, Pages: A21-A22, ISSN: 0959-9673
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