Objective: To determine the value of serological biomarkers of collagen degradation/turnover as serum markers of organ involvement in patients with systemic sclerosis (SSc). Methods: Serum samples were obtained from 79 SSc patients and 19 healthy control subjects. Types I to VI collagen turnover, e...
April 23, 2020
Journal:
Int J Rheum Dis
Author:
Kubo S, Siebuhr AS, Bay-Jensen AC, Juhl P, Karsdal MA, Satoh Y, Todoroki Y, Nakano K, Nakayamada S, Tanaka Y
Chronic obstructive pulmonary disease (COPD) is characterized by a slow heterogeneous progression. Therefore, improved biomarkers that can accurately identify patients with the highest likelihood of progression and therefore the ability to benefit from a given treatment, are needed. Elastin is an es...
March 11, 2020
Journal:
Sci Rep
Author:
Rønnow S, Langholm LL, Sand JMB, Thoracius-Using J, Leeming DJ, Manon-Jensen T, Tal-Singer R, Miller BE, Karsdal MA, Vestbo J
Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and lung tissue deterioration. Given the high vascularity of the lung, von Willebrand factor (VWF), a central component of wound healing initiation, has previously been assessed in COPD. VWF processing,...
March 9, 2020
Journal:
Int J Chron Obstruct Pulmon
Author:
Langholm LL, Rønnow S, bülow Sand JM, Leeming DJ, Talsinger R, Miller BE, Vestbo J, Karsdal MA, Manon-Jensen T
PURPOSE OF REVIEW: Biomarkers of remodeling represent a loose collection of features referring to several biological adaptations of the lung to cope with stressing factors. In addition, remodelling infers a dynamic process that would require a spatiotemporal resolution. This review focuses on differ...
Background: Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair process that may result in intra-airway accumulation of fibrin. Given that plasma fibrinogen is the only FDA approved biomarker that predicts mortality and COPD exacerbations, we hypothesized that...
December 2, 2019
Journal:
Lancet Respir Med
Author:
Manon-Jensen T, Langholm LL, Ronnow SR, Karsdal MA, Tal-Singer R, Vestbo J, Leeming DJ, Miller BE, bülow Sand JM
Introduction: Vimentin has shown to be highly implicated in cancer initiation and progression. Vimentin is often a target of post-translational modifications (PTMs) which can be disease specific, thus targeting these specific modifications can be of high biomarker potential. In this study we set out...
Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing th...
Idiopathic pulmonary fibrosis (IPF) is characterised by excessive extracellular matrix (ECM) deposition and remodelling. Measuring this activity provides an opportunity to develop tools capable of identifying individuals at-risk of progression. Longitudinal change in markers of ECM synthesis was ass...
July 12, 2019
Journal:
Respir Res.
Author:
Orlan LA, Duggan AR, Oballa E, Taggart SC, Simpson JK, Kangombe AR, Braybrooke R, Molyneaux PL, North B, Karkera Y, Leeming DJ, Karsdal MA, Nanthakumar CB, Fahy WA, Marshall RP, Jenkins RG, Maher TM
Cardiac fibrosis contributes to the development of heart failure in pulmonary hypertension. We aimed to assess the development of fibrosis and the effects of treatment with the anti-fibrotic agent pirfenidone in pressure overload induced right ventricular (RV) failure. Wistar rat weanlings were rand...
April 2, 2019
Journal:
Pulm Circ
Author:
Andersen S, Axelsen JB, Ringgaard S, Nyengaard JR, Holm Nielsen S, Genovese F, Karsdal MA, Hyldebrandt JA, Sørensen CB, de Man FS, Jan Bogaard H, Nielsen-kudsk JE, Andersen A
Studies with direct measures of body fat distribution are required to explore the association between central and general obesity to cancer risk in postmenopausal women. This study investigates the association between central obesity and general obesity to overall/site-specific cancer risk in postme...
March 29, 2019
Journal:
Sci Rep
Author:
Stanstrup LM, Nielsen HB, Pedersen BK, Karsdal MA, Blair JPM, Christensen JF, Bager CL
Chronic obstructive pulmonary disease (COPD) is characterized by a slow heterogeneous progression. Therefore, improved biomarkers that can accurately identify patients with the highest likelihood of progression and therefore the ability to benefit from a given treatment, are needed. Elastin is an es...
March 9, 2019
Journal:
Sci Rep
Author:
Ronnow SR, Langholm LL, Sand JMB, Thoracius-Ussing J, Leeming DJ, Manon-Jensen T, Tal-Singer R, Miller BE, Karsdal MA, Vestbo J
OBJECTIVES: Remodeling of the extracellular matrix (ECM) is a key event in different lung disorders, such as fibrosis and cancer. The most common cell type in the connective tissue is fibroblasts, which transdifferentiate into myofibroblasts upon activation. All myofibroblasts express α-SMA, which h...
February 12, 2019
Journal:
Transl Oncol
Author:
Holm Nielsen S, Willumsen N, Leeming DJ, Daniels SJ, brix s, Karsdal MA, Genovese F, Nielsen MJ
Myofibroblasts are the key effector cells responsible for excessive extracellular matrix deposition in multiple fibrotic conditions, including idiopathic pulmonary fibrosis (IPF). The PI3K/Akt/mTOR axis has been implicated in fibrosis, with pan-PI3K/mTOR inhibition currently under clinical evaluatio...
January 2, 2019
Journal:
Nature Communications
Author:
Woodcock HV, Eley JD, Platé M, Manthakumar CB, Martufi M, Peace S, Joberty G, Poeckel D, Good RB, Taylor AR, Zinn N, Redding M, Forty EJ, Hynds RE, Santon C, Karsdal MA, Maher TM, Bergamini G, Marshall RP, Blanchard AD, Mercer PF, Chambers RC
OBJECTIVES: Lysyl oxidase like 2 (LOXL2) is associated with poor prognosis in idiopathic pulmonary disease (IPF) and cancer. We developed an Enzyme-linked immunosorbent assay (ELISA) targeting the LOXL2 neo-epitope generated through the release of the signal peptide during LOXL2 maturation. DESIGN ...
November 30, 2018
Journal:
Biochem Biophys Rep
Author:
Leeming DJ, Willumsen N, Sand JM, Holm Nielsen S, Dasgupta B, Brodmerkel C, Bager CL, Karsdal MA
BACKGROUND: The role of the extracellular matrix (ECM) structure and remodeling thereof in lung diseases is gaining importance. Pathology-related changes in ECM turnover may result in deleterious changes in lung architecture, leading to disease in the small airways. Here, degradation fragments of ty...
October 1, 2018
Journal:
chest
Author:
papakonstantinou E, Kostikas K, Boersma W, Louis R, Milenkovik B, Aerts J, Sand JM, Wouters EFM, Rohde G, Prat C, Torres A, Welte T, Tamm M, Stolz D, Schumann D, Diana J Leeming, Karsdal MA
Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio...
September 10, 2018
Journal:
Biochem Biophys Res Commun
Author:
Gudmann NS, Manon-Jensen T, Sand JMB, Diefenbach C, Sun S, Danielsen A, Karsdal MA, Leeming DJ
Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio...
September 10, 2018
Journal:
Biochem Biophys Res Commun
Author:
Gudmann NS, Manon-Jensen T, Sand JM, Diefenbach C, Sun S, Danielsen A, Karsdal MA, Leeming DJ
The matricellular protein SPARC (secreted proteome acidic and rich in cysteine) is known to bind collagens and regulate fibrillogenesis. Cleavage of SPARC at a single peptide bond, increases the affinity for collagens up to 20-fold. To investigate if this specific cleavage has pathological relevance...
August 1, 2018
Journal:
Cancer biology therapy
Author:
Kehlet SN, Manon-Jensen T, Sun S, Brix S, Karsdal MA, Leeming DJ, Willumsen N
BACKGROUND: Idiopathic interstitial pneumonia (IIP) is characterized by an increased rate of extracellular matrix (ECM) remodeling resulting in fibrosis. Acute exacerbations of IIP represent periods of increased disease activity, thus we hypothesized that ECM remodeling was altered during acute exac...
May 4, 2018
Journal:
Respir Res
Author:
Sand JMB, Tanino Y, Karsdal MA, Nikaido T, Misa K, Sato Y, Togawa R, Wang X, Leeming DJ, Munakata M
OBJECTIVES: Fibrosis and cancer are characterized by extracellular matrix (ECM) remodeling. The basement membrane is mainly composed by collagen type IV and laminin. Tumstatin is a matrix metalloproteinase-9 (MMP-9) generated matrikine of collagen type IV α3 chain. We evaluated the potential of tums...
March 7, 2018
Journal:
Transl Oncol
Author:
Nielsen SH, Willumsen N, Brix S, Sun S, Manon-Jensen T, Karsdal MA, Genovese F
Type VII collagen is the main component of the anchoring fibrils connecting the basement membrane to the underlying interstitial matrix. Mutations in the type VII collagen gene cause dystrophic epidermolysis bullosa. Increased levels of type VII collagen in the skin have been reported in patients wi...
March 1, 2018
Journal:
Assay Drug Dev Technol
Author:
Sand JMB, Lamy P, Juhl P, Siebuhr AS, Iversen LV, Nawrocki A, Larsen MR, Domsic RT, Franchimont N, Chavez J, Karsdal MA, Leeming DJ
BACKGROUND: Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1. METHODS: One thousand COPD subjects from the observational,...
December 4, 2017
Journal:
BMC Pulm Med.
Author:
Leeming DJ, Byrjalsen I, Sand JMB, Bihlet AR, Lange P, Thal-Singer R, Miller BE, Karsdal MA, Vestbo J
Background: Decorin is one of the most abundant proteoglycans of the extracellular matrix and is mainly secreted and deposited in the interstitial matrix by fibroblasts where it plays an important role in collagen turnover and tissue homeostasis. Degradation of decorin might disturb normal tissue ho...
August 9, 2017
Journal:
BMC Pulm Med.
Author:
Karsdal MA, Leeming DJ, Brix S, Curran M, Brodmerkel C, Dasgupta B, Willumsen N, Bager CL, Kehlet SN
Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elast...
January 19, 2017
Journal:
Respir Res.
Author:
Bihlet AR, Karsdal MA, Sand JM, Leeming DJ, Roberts M, Bowler R, White WI
A high level of extracellular matrix (ECM) turnover characterizes several lung diseases with fibrotic features. Type III collagen is one of the most abundant collagens in lung parenchyma, and cathepsins play a role in lung pathology, being responsible for tissue remodeling. In this study, we explore...
BACKGROUND: There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated with mortalit...
October 4, 2016
Journal:
Respir Res.
Author:
Sand JM, Leeming DJ, Byrjalsen I, Bihlet AR, Lange P, Tal-Singer R, Miller BE, Karsdal MA, Vestbo J
OBJECTIVES: hronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that leads to excessive remodeling of the lung extracellular matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the blood. Serological markers assessing this have previously been a...
September 7, 2016
Journal:
Clin Biochem
Author:
Lange P, Leeming DJ, Karsdal MA, Midjord AK, Martinez G, Sand JM
BACKGROUND: Extracellular matrix (ECM) remodeling of the lung tissue releases protein fragments into the blood, where they may be detected as serologic surrogate markers of disease activity in COPD. Our goal was to assess the association of ECM turnover with severity and outcome of COPD. METHODS: I...
August 26, 2016
Journal:
Chest
Author:
Leeming DJ, Karsdal MA, Sand JM, Stolz D, Kristensen JH, Boersma W, Louis R, Milenkovic B, Kostikas K, Blasi F, Aerts J, Wouters EFM, Rohde G, Prat C, Torres A, Welte T, Roth M, Papakonstantinou E, Tamm M
BACKGROUND: Extracellular matrix (ECM) remodeling of the lung tissue releases protein fragments into the blood, where they may be detected as serologic surrogate markers of disease activity in COPD. Our goal was to assess the association of ECM turnover with severity and outcome of COPD. METHODS: I...
RATIONALE: Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant ...
August 1, 2016
Journal:
Thorax
Author:
Mercer PF, Woodcock HV, Eley JD, Platé M, Sulikowski MG, Durrenberger PF, Franklin L, Nanthakumar CB, Man Y2, Genovese F, McAnulty RJ, Yang S, Maher TM, Nicholson AG, Arbit E, Marshall RP, Lukey PT, Chambers RC
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