Publications
Find an abstract and a link to most of the publications produced by Nordic Bioscience
BACKGROUND Endotrophin, a collagen type VI–derived peptide, mediates metabolic dysregulation, inflammation, and fibrosis in animal models, but has not been studied in human heart failure (HF). METHODS We examined the association between circulating endotrophin and outcomes in participants sufferi...
September 21, 2022
Journal:
NEJM Evidence
Author:
Chirinos JA, Zhao L, Reese-Petersen AL, Cohen JB, Genovese F, Richards AM, Doughty RN, Diez J, Gonzalez A, Querejeta R, Zamani P, Nunez J, Wang Z, Ebert C, Kammerhoff K, Maranville J, Basso M, Qian C, Rasmussen DKG, Schafer PH, Seiffert D, Karsdal MA, Gordon DA, Ramirez-Valle F, Cappola TP
Background Aberrant extracellular matrix (ECM) deposition and remodelling is important in the disease pathogenesis of pulmonary fibrosis (PF). We characterised neoepitope biomarkers released by ECM turnover in lung tissue from bleomycin-treated rats and patients with PF and analysed the effects of ...
August 4, 2022
Journal:
Respiratory Research
Author:
Hesse C, Beneke V, Konzok S, Diefenbach C, Bülow Sand JM, Rønnow S, Karsdal MA, Jonigk D, Sewald K, Braun A, Leeming DJ, Wollin L
Background and aims: Liver fibrosis results from a prolonged wound healing response to continued injury with excessive production of extracellular proteins. In patients with chronic liver disease, the monitoring of liver fibrosis dynamics is of high interest. Whilst markers of fibrogenesis exist, ...
April 12, 2022
Journal:
Liver Int
Author:
Pehrsson M, Manon-Jensen T, Sun S, Villesen IF, Castane H, Joven J, Patel K, Goodman Z, Bay-Jensen AC, Mortensen JH, Karsdal MA, Leeming DJ, Nielsen MJ
Background: Extensive extracellular matrix (ECM) remodeling is a hallmark of metastatic pancreatic ductal adenocarcinoma (mPDA). We investigated fragments of collagen types III (C3M, PRO-C3), VI (PRO-C6), and VIII (C8-C), and versican (VCANM) in plasma as biomarkers for predicting progression-free s...
September 27, 2021
Journal:
J Transl Med.
Author:
Wang S, Bager CL, Karsdal MA, Chondros D, Taverna D, Willumsen N
Introduction: Enzymatic cross-linking of the collagens within the extracellular matrix (ECM) catalyzed by enzymes such as lysyl oxidase (LOX) and lysyl oxidase like-enzymes 1-4 (LOXL), transglutaminase 2 (TG2), and peroxidasin (PXDN) contribute to fibrosis progression through extensive collagen cros...
August 24, 2021
Journal:
Expert Rev Mol Diagn
Author:
Pehrsson M, Mortensen JH, Manon-Jensen T, Bay-Jensen AC, Karsdal MA, Davies MJ
Background & aims: Progressive fibrosis has been identified as the major predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). Several biomarkers are currently being evaluated for their ability to substitute the liver biopsy as the reference standard. Recent clinical...
July 10, 2021
Journal:
JHEP Rep
Author:
Erhardtsen E, Rasmussen DGK, Frederiksen P, Leeming DJ, Gluud LL, Karsdal MA, Aithal GP, Shattenberg JM, Shevell DE
Background: Renal fibrosis is the hallmark of chronic kidney disease (CKD) and characterized by an imbalanced extracellular matrix remodeling. Endotrophin (ETP) is a signaling molecule released from collagen type VI (COL VI). ETP can be measured by the PRO-C6 assay, which quantifies the levels of CO...
April 29, 2021
Journal:
Nephrol Dial Transplant
Author:
Sparding N, Rasmussen DGK, Karsdal MA, Neprasova M, Maixnerova D, Satrapova V, Frausova D, Hornum M, Bartonova L, Honsova E, Kollar M, Koprivova H, Hruskova Z, Tesar V, Genovese F
Angina and no obstructive coronary artery disease (CAD) have an unfavorable prognosis, possibly due to diffuse myocardial fibrosis (DMF). In DMF the proteoglycans biglycan and versican are actively remodeled by matrix metalloproteinase. We investigated biglycan and versican in females with angina an...
March 1, 2021
Journal:
J Cardiovasc Transl Res
Author:
Mygind ND, Holm Nielsen S, Michelsen MM, Pena A, Bechsgaard DF, Bove KB, Karsdal MA, Vejlstrup N, Prescott E, Kastrup J, Genovese F, Nielsen Bay H, Suhrs HE
Purpose: Non-invasive biomarkers for diagnosing and prognosing hepatocellular carcinoma (HCC) are urgently needed. Cirrhosis is present in 80-90% of HCC patients. Cirrhosis is characterized by deposition and cross-linking of collagens that have crucial roles in HCC initiation and progression. We eva...
November 20, 2020
Journal:
J Hepatocell Carcinoma
Author:
Jensen C, Holm Nielsen S, Eslam M, Genovese F, Nielsen MJ, Vongsuvanh R, Uchila R, van der Poorten D, George J, Karsdal MA, Leeming DJ, Willumsen N.
A T-cell permissive tumor microenvironment, characterized by the presence of activated T cells and low fibrotic activity is crucial for response to immune checkpoint inhibitors (ICIs). Granzyme B has been shown to promote T-cell migration through the basement membrane by the degradation of type IV c...
September 20, 2020
Journal:
Cancers (Basel)
Author:
Jensen C, Sinkeviciute D, Madsen DH, Önnerfjord P, Hansen M, Schmidt H, Karsdal MA, Svane IM, Willumsen N
Fibrosis is often heterogeneously distributed, and classical biopsies do not reflect this. Noninvasive methods for renal fibrosis have been developed to follow chronic kidney diseases (CKD) and to monitor anti-fibrotic therapy. In this study, we combined two approaches to assess fibrosis regression ...
August 14, 2020
Journal:
Pharmaceutics
Author:
Nielsen PM, Mariager CØ, Rasmussen DGK, Mølmer M, Karsdal MA, Laustsen C, Nørregaard R, Genovese F
Purpose: Renal tubulointerstitial fibrosis is strongly linked to the progressive decline of renal function seen in chronic kidney disease. State-of-the-art noninvasive diagnostic modalities are currently unable to detect the earliest changes associated with the onset of fibrosis. This study was unde...
May 25, 2020
Journal:
Magn Reson Med
Author:
Nielsen PM, Mariager CØ, Mølmer M, Sparding N, Genovese F, Karsdal MA, Nørregaard R, Bertelsen LB, Laustsen C
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
Amylin treatment improves body weight and glucose control, although it is limited by a short action and need for high doses. Dual amylin and calcitonin receptor agonists (DACRAs) are dual amylin and calcitonin receptor agonists with beneficial effects beyond those of amylin. However, to what extent ...
April 21, 2020
Journal:
J Pharmacol Exp Ther
Author:
Larsen AT, Sonne N, Andreassen KV, Karsdal MA, Henriksen K
There is an unmet need for high-quality liquid biomarkers that can safely and reproducibly predict the stage of fibrosis and the outcomes of chronic liver disease (CLD). The requirement for such markers has intensified because of the high global prevalence of diseases such as non-alcoholic fatty liv...
April 9, 2020
Journal:
Liver Int
Author:
Karsdal MA, Daniels SJ, Nielsen SH, Bager CL, Rasmussen DGK, Loomba R, Surabattula R, Villesen IF, Luo Y, Gudmann NS, Nielsen MJ, George J, Christian R, Leeming DJ, Schuppan D, Shevell DE
Diabetic kidney disease is a worldwide epidemic, and therapies are incomplete. Clinical data suggest that improved renal outcomes by Na+-glucose cotransporter 2 inhibitor (SGLT2i) are partly beyond their antihyperglycemic effects; however, the mechanisms are still elusive. Here, we investigated the ...
April 1, 2020
Journal:
AM J Physiol Renal Physiol
Author:
Hodrea J, Balogh DB, Hosszu A, Lenart L, Besztercei B, Sparding N, Genovese F, Wagner LJ, Szabo AJ, Fekete A, Koszegi S
Background Tubulointerstitial fibrosis is a major pathological feature in chronic kidney disease (CKD) and collagen type III (COL3) is a major component of the renal fibrotic scar. We hypothesized that a dysregulated turnover of COL3 is an important determinant of CKD progression. We assessed the r...
January 14, 2020
Journal:
ERA-EDTA Clinical Kidney Journal
Author:
Genovese F, Rasmussen DGK, Jesky M, Fenton A, Cockwell P, Karsdal MA, Ferro CJ
Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are common causes of chronic liver disease. The overlap between ALD and NAFLD suggests the existence of metabolic steatohepatitis. Development of in vivo models that reflect various aspects of human steatohepatitis is essenti...
January 6, 2020
Journal:
Am J Physiol Gastrointest Liver Physiol
Author:
Daniels SJ, Leeming DJ, Detlefsen S, Bruun MF, Hjuler ST, Henriksen K, Hein P, Krag A, Karsdal MA, Nielsen MJ, Brockbank S, Cruwys S
An altered liver microenvironment characterized by a dysregulated extracellular matrix (ECM) supports the development and progression of hepatocellular carcinoma (HCC). The development of experimental platforms able to reproduce these physio-pathological conditions is essential in order to identify ...
December 28, 2019
Journal:
Cells
Author:
Mazza G, Telese A, Al-Akkad W, Frenguelli L, Levi A, Marrali M, Longato L, Thanapirom K, Vilia MG, Lombardi B, Crowley C, Crawford M, Karsdal MA, Leeming DJ, Marrone G, Bottcher K, Robinson B, Del Rio Hernandez A, Tamburrino D, Spoletini G, Malago M, Hall AR, Godovac-Zimmermann J, Luong TV, De Coppi P, Pinzani M, Rombouts K
Is liver fibrosis just liver fibrosis? Or do the subtype of collagen, its spatial localization in the liver, its cell of origin, and the time point at which it is synthesized also matter? It is important, since the various collagen subtypes hold different informative values regarding reparative proc...
December 18, 2019
Journal:
Hepatology
Author:
Karsdal MA, Detlefsen S, Daniels SJ, Nielsen MJ, Krag A, Schuppan D
The involvement of fibrosis as an underlying pathology in heart diseases is becoming increasingly clear. In recent years, fibrosis has been granted a causative role in heart diseases and is now emerging as a major contributor to Atrial Fibrillation (AF) pathogenesis. AF is the most common arrhythmia...
November 6, 2019
Journal:
Matrix Biol
Author:
Reese-Petersen AL, Olesen MS, Karsdal MA, Svendsen JH, Genovese F
Renal fibrosis is a hallmark of chronic kidney disease (CKD) caused by an imbalance between formation and degradation of extracellular matrix proteins. We investigated the collagen turnover profile of 81 non-dialysis CKD stage 2-5 patients by measuring peptides reflecting formation and degradation o...
November 5, 2019
Journal:
Sci Rep
Author:
Boesby L, Nielsen SH, Teepel M, Birot S, Karsdal MA, Kamper Al, Genovese F, Rasmussen DGK
Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups...
October 25, 2019
Journal:
Nat Med
Author:
Moroni F, Dwyer BJ, Graham C, Pass C, Bailey L, Ritchie L, Mitchell D, Glover A, Lauire A, Doig S, Hargreaves E, Fraser AR, Turner ML, Cambpell JDM, McGowan NWA, Barry J, Moore JK, Hayes PC, Leeming DJ, Nielsen MJ, Musa K, Fallowfield JA, Forbes SJ
BACKGROUND: Lifestyle modifications remain the cornerstone of treatment in non-alcoholic fatty liver disease (NAFLD). However, they requently fail related to the inability of patients to implement lasting changes. AIMS: To evaluate the effects of a short, web-based, individualised exercise program ...
October 16, 2019
Journal:
Aliment Pharmacol Ther.
Author:
Huber Y, Pfirrmann D, Gebhardt I, Labenz C, Gehrke N, Straub C, Ruckes C, Bantel H, Belda E, Clément K, Leeming DJ, Karsdal MA, Galle PR, Simon P, Schattenberg JM
Following liver transplantation (LT), 10-30% of patients develop recurrent cirrhosis (RC). There is an urgent need for predictive non-invasive markers for improved monitoring of these patients. Here we studied extracellular matrix biomarkers as predictors of RC after LT. Forty-seven LT patients were...
October 16, 2019
Journal:
Sci Rep
Author:
Nielsen MJ, Villesen IF, Gudmann NS, Leeming DJ, Krag A, Karsdal MA, Zimmermann T, Schuppan D
BACKGROUND:Maintenance of kidney function in kidney allografts remains a challenge, as the allograft often progressively develops fibrosis after kidney transplantation. Fibrosis is caused by the accumulation of extracellular matrix proteins like type I and III collagen (COL I and III) that replace t...
August 1, 2019
Journal:
Nephrol Dial Transplant
Author:
Nielsen PM, Nielsen SH, Kerulf-Lassen C, Karsdal MA, Genovese F, Nørregaard R, Kasab-Oglo ÖY, Rasmussen DGK
Background and aims: Although combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recent studies ...
July 11, 2019
Journal:
PLoS One
Author:
Dold L, Nielsen MJ, Praktiknjo M, Schwarzer-Zander C, Boesecke C, Schierwagen R, Mohr R, Wasmuth JC, Jansen C, Bischoff J, Rockstroh J, Karsdal MA, Leeming DJ, Trebicka JK
There is an unmet need for non-invasive biomarkers in non-alcoholic fatty liver disease (NAFLD) that can diagnose advanced disease and identify patients suitable for clinical trials. The PRO-C3 collagen neo-epitope is a putative direct marker of fibrogenesis. We assessed the performance of PRO-C3 in...
July 4, 2019
Journal:
JHEP Rep
Author:
Boyle M, Schattenberg JM, Ratziu V, Bugianessi E, Petta S, Oliveira CP, Govaere O, Yournes R, McPherson S, Bedossa P, Nielsen MJ, Kendrick, Anstee QM, Karsdal MA, Tiniakos D, Leeming DJ
OBJECTIVE: This study assessed the utility of plasma fragments of propeptides of type III (PRO-C3), V (PRO-C5), and VI (PRO-C6) procollagen for the detection of liver fibrosis in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Patients with T2DM (n = 191) underwent an or...
July 1, 2019
Journal:
Diabetes Care
Author:
Bril F, Leeming DJ, Karsdal MA, Kalavalapalli S, Darb D, Lai J, Rabe M, Cusi K
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, Andersen A, Bogaard JH, Nielsen-Kudsk JE
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