L Larsen

Publications (3)2.02 Total impact

• Source

  Available from: Efstathios Vassiliadis

  Article: Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice.

  N Barascuk, E Vassiliadis, Q Zheng, Y Wang, W Wang, L Larsen, L M Rasmussen, M A Karsdal
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  ABSTRACT: Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELISA) developed to measure a specific MMP12-derived fragment of mimecan, MMCN-151, in apolipoprotein-E knockout (ApoE-KO) mice. A mouse monoclonal antibody raised against MMCN-151 was used to develop a competitive ELISA. The assay was validated using samples from 20 ApoE-KO and 20 wild type [C57 BL/6] male mice fed a normal or high-fat diet (HFD) for up to 20 weeks. The technical reliability of the assay was established with intra-assay variability <2% and inter-assay variability <10%. The lowest limit of quantification of MMCN-151 was 0.5 ng/ml. ApoE-KO mice fed a HFD for 20 weeks had four-fold increased circulating levels of MMCN-151 compared to baseline, whereas MMCN-151 levels in control mice on HFD increased two-fold compared with baseline. After 10 weeks of a HFD, a significant difference in MMCN-151 levels was observed between ApoE-KO and control mice (P = 0.005) and became more significant at 20 weeks (P = 0.002). The newly developed assay is a reliable detector of MMCN-151 levels which ultimately may be useful indicators of arterial remodeling in patients affected by atherosclerotic disease.
  Biomarker insights 01/2011; 6:97-106.
• Article: A novel assay for extracellular matrix remodeling associated with liver fibrosis: An enzyme-linked immunosorbent assay (ELISA) for a MMP-9 proteolytically revealed neo-epitope of type III collagen.

  N Barascuk, S S Veidal, L Larsen, D V Larsen, M R Larsen, J Wang, Q Zheng, R Xing, Y Cao, L M Rasmussen, M A Karsdal
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  ABSTRACT: Accumulation of extracellular matrix (ECM) components and increased matrix-metalloprotease (MMPs) activity are hallmarks of fibrosis. We developed an ELISA for quantification of MMP-9 derived collagen type III (CO3) degradation. A monoclonal antibody targeting a specific MMP-9 cleaved fragment of CO3 was used for development of a competitive ELISA. The assay was investigated in serum and tissues from bile duct ligated rats (BDL). The ELISA showed no cross-reaction with either intact CO3, or other collagens. The intra- and inter-assay CV were below 10%. Liver fibrosis was demonstrated in BDL animals by semi quantitative scoring (P<0.0001). Serum levels of CO3-610 increased 2.5 fold in BDL animals (P<0.001). The CO3-610 levels were 5 fold higher in ex vivo cultures of fibrotic livers compared to controls (P<0.001). We have developed a novel ELISA for measuring a specific fragment CO3 generated by MMP-9 important in pathogenesis of liver fibrosis.
  Clinical biochemistry 04/2010; 43(10-11):899-904. · 2.02 Impact Factor
• Article: A novel assay for extracellular matrix remodeling associated with liver fibrosis: An enzyme-linked immunosorbent assay (ELISA) for a MMP-9 proteolytically revealed neo-epitope of type III collagen

  N. Barascuk, S.S. Veidal, L. Larsen, D.V. Larsen, M.R. Larsen, J. Wang, Q. Zheng, R. Xing, Y. Cao, L.M. Rasmussen, M.A. Karsdal
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  ABSTRACT: ObjectivesAccumulation of extracellular matrix (ECM) components and increased matrix-metalloprotease (MMPs) activity are hallmarks of fibrosis. We developed an ELISA for quantification of MMP-9 derived collagen type III (CO3) degradation.Design andmethodsA monoclonal antibody targeting a specific MMP-9 cleaved fragment of CO3 was used for development of a competitive ELISA. The assay was investigated in serum and tissues from bile duct ligated rats (BDL).ResultsThe ELISA showed no cross-reaction with either intact CO3, or other collagens. The intra- and inter-assay CV were below 10%. Liver fibrosis was demonstrated in BDL animals by semi quantitative scoring (P < 0.0001). Serum levels of CO3-610 increased 2.5 fold in BDL animals (P < 0.001). The CO3-610 levels were 5 fold higher in ex vivo cultures of fibrotic livers compared to controls (P < 0.001).ConclusionWe have developed a novel ELISA for measuring a specific fragment CO3 generated by MMP-9 important in pathogenesis of liver fibrosis.
  Clinical Biochemistry.