The Citrullinated and MMP-degraded Vimentin Biomarker (VICM) Predicts Early Response to Anti-TNFα Treatment in Crohn's Disease
Background: In Crohn's disease (CD), 10% to 40% of patients do not respond to anti-tumor necrosis factor-α (TNFα) treatment. Currently, there are no biomarkers with adequate sensitivity to separate responders from nonresponders at an early stage.
Aim: The aim of this study was to investigated whe…
Journal:
Authors:
- Mortensen JH,
- Van Haaften WT,
- Karsdal MA,
- Bay-Jensen AC,
- Olinga P,
- Grønbæk H,
- Hvas CL,
- Manon-Jensen T,
- Dijkstra G,
- Dige A,
Increased Von Willebrand Factor Processing in COPD, Reflecting Lung Epithelium Damage, Is Associated With Emphysema, Exacerbations and Elevated Mortality Risk
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,…
Journal:
Authors:
- Langholm LL,
- Rønnow S,
- bülow Sand JM,
- Leeming DJ,
- Talsinger R,
- Miller BE,
- Vestbo J,
- Karsdal MA,
- Manon-Jensen T,
End-product of fibrinogen is elevated in emphysematous chronic obstructive pulmonary disease and is predictive of mortality in the ECLIPSE cohort.
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 tha…
Journal:
Authors:
- Manon-Jensen T,
- Langholm LL,
- Ronnow SR,
- Karsdal MA,
- Tal-Singer R,
- Vestbo J,
- Leeming DJ,
- Miller BE,
- bülow Sand JM,
Mechanisms of vascular permeability and remodeling associated with hemarthrosis in factor VIII-deficient mice.
Vascular remodeling associated with hemophilic arthropathy (HA) may contribute to bleed propagation, but the mechanisms remain poorly understood.
OBJECTIVES:
To explore molecular mechanisms of HA and the effects of hemostasis correction on synovial vascular remodeling after joint injury in hypoc…
Journal:
Authors:
- Cooke EJ,
- Wyseure T,
- Zhou JY,
- Gopal S,
- Nasmran CA,
- Fisch KM,
- Manon-Jensen T,
- Karsdal MA,
- Mosnier LO,
- Von Drygalski A,
The intestinal tissue homeostasis - the role of extracellular matrix remodeling in inflammatory bowel disease
Introduction: Extracellular matrix (ECM) remodeling of the intestinal tissue is important in inflammatory bowel disease (IBD) due to the extensive mucosal remodeling. There are still gaps in our knowledge as to how ECM remodeling is related to intestinal epithelium homeostasis and healing of the int…
Journal:
Authors:
- Mortensen JH,
- Lindholm M,
- Langholm LL,
- Kjeldsen J,
- Bay-Jensen AC,
- Karsdal MA,
- Manon-Jensen T,
Serological Assessment of the Quality of Wound Healing Processes in Crohn's Disease.
BACKGROUND AND AIMS:
Crohn's disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot forma…
Journal:
Authors:
- Sun S,
- Karsdal MA,
- Mortensen JH,
- Luo Y,
- Kjeldsen J,
- Krag A,
- Jensen MD,
- Bay-Jensen AC,
- Manon-Jensen T,
Specific elastin degradation products are associated with poor outcome in the ECLIPSE COPD cohort
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…
Journal:
Authors:
- Ronnow SR,
- Langholm LL,
- Sand JMB,
- Thoracius-Ussing J,
- Leeming DJ,
- Manon-Jensen T,
- Tal-Singer R,
- Miller BE,
- Karsdal MA,
- Vestbo J,
GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro
C-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe…
Journal:
Authors:
- Löfvall H,
- Katri A,
- Dabrowska A,
- Karsdal MA,
- Luo Y,
- He Y,
- Manon-Jensen T,
- Dziegiel MH,
- Bay-Jensen AC,
- Thudium CS,
- Henriksen K,
Enhanced processing of von Willebrand factor reflects disease severity and discriminates severe portal hypertension in cirrhosis
OBJECTIVES:
Portal hypertension in cirrhosis is associated with endothelial dysfunction, impaired wound healing, and decreased platelet count. Increased von Willebrand factor (VWF) formation has been suggested as a compensatory mechanism, but the role of VWF processing has not been directly assesse…
Journal:
Authors:
- Langholm LL,
- Manon-Jensen T,
- Karsdal MA,
- Bendtsen F,
- Leeming DJ,
- Møller S,
Initiation of the Wound Healing Cascade in Inflammatory Bowel Disease: Assessment of Von Willebrand Factor ADAMTS-13 Processing and Formation in Crohn’s Disease
Background: Crohn’s disease (CD) is a chronic inflammatory condition of the intestinal tract resulting in severe intestinal tissue
damage. The concept of mucosal healing has therefore gained significant interest as a therapeutic end point in the treatment of
inflammatory bowel disease (IBD). Given…
Authors:
- Manon-Jensen T,
- Langholm LL,
- Sun S,
- Mortensen JH,
- He Y,
- Krag A,
- Jensen MD,
- Bay-Jensen AC,
- Kjeldsen J,
- Karsdal MA,
Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis.
OBJECTIVE:
Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of OA, of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type X collagen t…
Journal:
Authors:
- He Y,
- Manon-Jensen T,
- Arendt-Nielsen L,
- Petersen KK,
- Christiansen T,
- Samuels J,
- Abramson S,
- Karsdal MA,
- Attur M,
- Bay-Jensen AC,
Lung tissue destruction by proteinase 3 and cathepsin G mediated elastin degradation is elevated in chronic obstructive pulmonary disease.
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…
Journal:
Authors:
- Gudmann NS,
- Manon-Jensen T,
- Sand JMB,
- Diefenbach C,
- Sun S,
- Danielsen A,
- Karsdal MA,
- Leeming DJ,
Lung tissue destruction by proteinase 3 and cathepsin G mediated elastin degradation is elevated in chronic obstructive pulmonary disease
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…
Journal:
Authors:
- Gudmann NS,
- Manon-Jensen T,
- Sand JM,
- Diefenbach C,
- Sun S,
- Danielsen A,
- Karsdal MA,
- Leeming DJ,
A fragment of SPARC reflecting increased collagen affinity shows pathological relevance in lung cancer - implications of a new collagen chaperone function of SPARC
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…
Journal:
Authors:
- Kehlet SN,
- Manon-Jensen T,
- Sun S,
- Brix S,
- Karsdal MA,
- Leeming DJ,
- Willumsen N,
Tumstatin, a Matrikine Derived from Collagen Type IVα3, is Elevated in Serum from Patients with Non-Small Cell Lung Cancer
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…
Journal:
Authors:
- Nielsen SH,
- Willumsen N,
- Brix S,
- Sun S,
- Manon-Jensen T,
- Karsdal MA,
- Genovese F,
The endothelial specific isoform of type XVIII collagen correlates to annual bleeding rate in haemophilia patients
INTRODUCTION:
The medical need in the haemophilic (HF) field to reduce bleeding incidents requires measurement of the annual bleeding rate (ABR) in haemophiliacs. Vascular rupture is associated with damage to the vascular endothelium causing exposure of the basement membrane. Endothelial cells and …
Journal:
Authors:
- Kjeld NG,
- Hua B,
- Karsdal MA,
- Sun S,
- Manon-Jensen T,
Ulcerative colitis, Crohn's disease, and irritable bowel syndrome have different profiles of extracellular matrix turnover, which also reflects disease activity in Crohn's disease
BACKGROUND:
Increased protease activity is a key pathological feature of inflammatory bowel disease (IBD). However, the differences in extracellular matrix remodelling (ECM) in Crohn's disease (CD) and ulcerative colitis (UC) are not well described. An increased understanding of the inflammatory pr…
Journal:
Authors:
- Bay-Jensen AC,
- Karsdal MA,
- Krag A,
- Kjeldsen J,
- Klinge LG,
- Hägglund P,
- Jensen MD,
- Manon-Jensen T,
- Mortensen JH,
Increased basement membrane turnover and strongly attenuated interstitial matrix turnover is a key pathological feature of haemophilia
Altered extracellular matrix (ECM) turnover is a central pathological feature of many diseases. The ECM is a meshwork of molecules that provides structural support to cells throughout the body. It consists mainly of two membranes: the interstitial matrix, which is present between parenchymal cells i…
Journal:
Authors:
- Manon-Jensen T,
- Hua BL,
- Olsen EHN,
- Sun S,
- Gudme CN,
- Li J,
- Lei W,
- Vandahl B,
- Roepstorff K,
- Kjelgaard-Hansen M,
- Zhao Y,
- Karsdal MA,
The good and the bad collagens of fibrosis - Their role in signaling and organ function
Usually the dense extracellular structure in fibrotic tissues is described as extracellular matrix (ECM) or simply as collagen. However, fibrosis is not just fibrosis, which is already exemplified by the variant morphological characteristics of fibrosis due to viral versus cholestatic, autoimmune or…
Journal:
Authors:
- Karsdal MA,
- Nielsen SH,
- Leeming DJ,
- Langholm LL,
- Nielsen MJ,
- Manon-Jensen T,
- Siebuhr AS,
- Gudmann NS,
- Rønnow S,
- Sand JM,
- Daniels SJ,
- Mortensen JH,
- Schuppan D,
Serological biomarkers detect active joint destruction and inflammation in patients with haemophilic arthropathy
INTRODUCTION:
Progressive arthropathy caused by recurrent joint bleeds is a severe complication in haemophilia.
AIM:
We investigated whether biomarkers of cartilage and bone degradation, and inflammation were altered in haemophilia patients and whether these biomarkers could identify haemophili…
Journal:
Authors:
- Hua B,
- Olsen EHN,
- Sun S,
- Gudme CN,
- Wang L,
- Vandahl B,
- Roepstorff K,
- Kjelgaard-Hansen M,
- Sørensen BB,
- Zhao Y,
- Karsdal MA,
- Manon-Jensen T,
Altered collagen turnover in factor VIII-deficient rats with hemophilic arthropathy identifies potential novel serological biomarkers in hemophilia
ESSENTIALS:
Joint bleeding in hemophilia may induce significant remodeling of the extracellular matrix. Biomarkers of collagen turnover were investigated in a F8-/- rat model of hemophilic arthropathy. Biomarkers of cartilage degradation increased significantly during development of arthropathy. B…
Journal:
Authors:
- Manon-Jensen T,
- Karsdal MA,
- Nielsen LN,
- Kjelgaard-Hansen M,
- Vandahl B,
- Olsen EHN,
- Enoksson M,
- Roepstorff K,
Intercritical circulating levels of neo-epitopes reflecting matrixmetalloprotease-driven degradation as markers of gout and frequent gout attacks
OBJECTIVE:
Recurrent flares constitute the main clinical burden of gout. Our aim was to assess whether biomarkers measuring MMP tissue degradation could be used as markers of frequent gout flares.
METHODS:
Fasting plasma samples from 112 men with gout and 170 controls, along with serum samples …
Journal:
Authors:
- Valdes AM,
- Manon-Jensen T,
- Abhishek A,
- Jenkins W,
- Siebuhr AS,
- Karsdal MA,
- Doherty S,
- Zhang W,
- Richardson H,
- Doherty M,
- Bay-Jensen AC,
Collagen-mediated hemostasis
Collagens mediate essential hemostasis by maintaining the integrity and stability of the vascular wall. Imbalanced turnover of collagens by uncontrolled formation and/or degradation may result in pathologic conditions such as fibrosis. Thickening of the vessel wall because of accumulation of collage…
Journal:
Authors:
- Manon-Jensen T,
- Kjeld NG,
- Karsdal MA,
Collagen and tissue turnover as function of age - implications for fibrosis
BACKGROUND:
The extracellular matrix (ECM) is the backbone of all tissues. It is a complex grid consisting of multiple structural proteins which each play a vital role for the function and maintenance of normal tissue function. In development and growth, tissue is being formed and elaborated (tissu…
Journal:
Authors:
- Karsdal MA,
- Genovese F,
- Madsen EA,
- Manon-Jensen T,
- Schuppan D,
Novel insights into the function and dynamics of extracellular matrix in liver fibrosis
Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential…
Authors:
- Karsdal MA,
- Manon-Jensen T,
- Genovese F,
- Kristensen JH,
- Nielsen MJ,
- Sand JM,
- Hansen NU,
- Bay-Jensen AC,
- Bager CL,
- Krag A,
- Blanchard A,
- Krarup H,
- Leeming DJ,
- Schuppan D,