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
Background: Patients with atherosclerosis have a high risk of cardiovascular events and death. Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix proteins in the intima. We hypothesized that dysregulated remodeling of the basement membrane proteins may be asso...
November 6, 2018
Journal:
J am heart assoc
Author:
Nielsen SH, Tengryd C, Edsfeldt A, Brix S, Genovese F, Bengtsson E, Karsdal MA, Leeming DJ, Nilsson J, Goncalves I
BACKGROUND: Patients with chronic kidney disease (CKD) have increased risk of development of end-stage renal disease (ESRD) and early mortality. Fibrosis is the central pathogenic process in CKD and is caused by dysregulated extracellular matrix (ECM) remodeling. The laminin γ1 chain (LAMC1) is a co...
October 1, 2018
Journal:
PLoS One
Author:
Holm Nielsen S, Brix S, Jesky M, Fenton A, Ferro CJ, Karsdal MA, Genovese F, Cockwell P, Rasmussen DGK
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
AIM: Collagens are major cardiac extracellular matrix components, known to be actively remodelled and accumulated during diffuse myocardial fibrosis. We evaluated whether accelerated collagen turnover described by neo-epitope biomarkers reflecting collagen formation and degradation separates patient...
May 25, 2018
Journal:
Eur J Prev Cardiol
Author:
Nielsen SH, Mygind ND, Michelsen MM, Bechsgaard DF, Suhrs HE, Genovese F, Brix S, Karsdal MA, Prescott E, Kastrup J, Nielsen Bay H
BACKGROUND: Truncated tau appears to be specifically related to disease pathology and recent studies have shown the presence and elevation of several truncated tau species in Cerebrospinal fluid (CSF) of subjects with Alzheimer\u0027s disease (AD); however, the relevance of truncated Tau measurement...
April 11, 2018
Journal:
PLoS One
Author:
Neergaard JS, Dragsbæk K, Christiansen C, Karsdal MA, Brix S, Henriksen K
The extracellular matrix (ECM) plays a vital role in maintaining normal tissue function. Collagens are major components of the ECM and there is a tight equilibrium between degradation and formation of these proteins ensuring tissue health and homeostasis. As a consequence of tissue turnover, small c...
March 29, 2018
Journal:
PLoS One
Author:
Kehlet SN, Willumsen N, Armbrecht G, Dietzel R, Brix S, Henriksen K, Karsdal MA
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
BACKGROUND: Identification of subjects with a progressive disease phenotype is an urgent need in the pharmaceutical industry where most of the recent clinical trials in Alzheimer\u0027s disease have failed. OBJECTIVES: The objective of this study was to identify subgroups of individuals with object...
December 1, 2017
Journal:
J Prev Alzheimers Dis
Author:
Neergaard JS, Dragsbæk K, Christiansen C, Karsdal MA, Brix S, Henriksen K
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
There has been limited success with blood-based biomarkers of neurodegeneration. One perceived reason is that blood has no direct contact to the brain. Recently developed blood-based biomarkers of tau-degradation have shown promise as potential tools for peripheral assessment of neurodegeneration; h...
May 10, 2017
Journal:
Neurochem Int
Author:
Karsdal MA, Henriksen K, Brix S, Workman CT, Christiansen C, Dragsbæk K, Neergaard JS, Nielsen Bay H
Kidney allograft failure due to chronic injury/rejection remains the main cause of graft loss in renal transplant recipients (RTR). Here, we investigated whether specific biomarkers of extracellular matrix (ECM) turnover are associated with allograft function and chronic kidney disease (CKD) stage i...
April 21, 2017
Journal:
PLoS One
Author:
Stribos EGD, Nielsen SH, Brix S, Karsdal MA, Seelen MA, van Goor H, Bakker SJL, Olinga P, Mutsaers HAM, Genovese F
Dementia and type 2 diabetes are both characterized by long prodromal phases, challenging the study of potential risk factors and their temporal relation. The progressive relation among metabolic syndrome, insulin resistance (IR), and dementia has recently been questioned, wherefore the aim of this ...
April 7, 2017
Journal:
Diabetes Care
Author:
Neergaard JS, Dragsbæk K, Christiansen C, Brix S, Karsdal MA, Henriksen K, Nielsen Bay H
Background: Hyperglycaemia increases the risk of type 2 diabetes, heart disease and stroke, and is influenced by weight. However, the impact of preceding weight change on blood glycemia levels in late-life is less well understood. Aim: We studied the interplay between weight change and risk of hype...
March 6, 2017
Journal:
Aging Clin Exp Res
Author:
Dragsbæk K, Neergaard JS, Christiansen C, Karsdal MA, Beck-Nielsen H, Brix S, Henriksen K
The prognostic value of the metabolic syndrome (MetS) is believed to vary with age. With an elderly population expecting to triple by 2060, it is important to evaluate the validity of MetS in this age group. We examined the association of MetS risk factors with later risk of type 2 diabetes (T2DM) a...
September 15, 2016
Journal:
Medicine (Baltimore)
Author:
Dragsbæk K", Neergaard JS, Laursen JM, Hansen HB, Christiansen C, Beck-Nielsen H, Karsdal MA, Brix S, Henriksen K
During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of prote...
July 28, 2016
Journal:
Scientific Reports, Nature
Author:
Kehlet SN, Sanz-Pamplona R, Brix S, Leeming DJ, Karsdal MA, Moreno V
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