Renal System, Chronic Renal Disease, Extracellular Matrix Research, Biomarker position
25. May 2020
Hyperpolarized [1- 13 C] Alanine Production: A Novel Imaging Biomarker of Renal Fibrosis
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…
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Journal:
Authors:
- Nielsen PM,
- Mariager CØ,
- Mølmer M,
- Sparding N,
- Genovese F,
- Karsdal MA,
- Nørregaard R,
- Bertelsen LB,
- Laustsen C,
Cardiovascular System, Extracellular Matrix Research, Atherosclerosis
1. May 2020
Exploring the Role of Extracellular Matrix Proteins to Develop Biomarkers of Plaque Vulnerability and Outcome
Cardiovascular disease (CVD) is the most common cause of death in industrialized countries. One underlying cause is atherosclerosis, which is a systemic disease characterized by plaques of retained lipids, inflammatory cells, apoptotic cells, calcium and extracellular matrix (ECM) proteins in the ar…
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Journal:
Authors:
- Nielsen SH,
- Jonasson L,
- Kalogeropoulos K,
- Karsdal MA,
- Reese-Petersen AL,
- Auf dem Keller U,
- Genovese F,
- Nilsson J,
- Goncalves I,
Gastrointestinal, Extracellular Matrix Research
3. Apr 2020
A Fragment of Collagen Type VI alpha-3 Chain Is Elevated in Serum From Patients With Gastrointestinal Disorders
Extracellular matrix (ECM) remodeling is a hallmark of the pathology of gastrointestinal disorders. Collagen type VI (COL6) is produced by fibroblasts, and the COL6 α3-chain has shown to be elevated in patients with ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC). Measuring…
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Journal:
Authors:
- Nielsen SH,
- Mortensen JH,
- Willumsen N,
- guldager Kring Rasmussen D,
- Mogensen DJ,
- Di Sabatino A,
- Mazza G,
- Jørgensen LN,
- giuffrida P,
- Pinzani M,
- Klinge L,
- Kjeldsen J,
- Leeming DJ,
- Karsdal MA,
- Genovese F,
Renal System, Endocrinology, Type 2-Diabetes, Type 1-Diabetes
1. Apr 2020
Reduced O-GlcNAcylation and Tubular Hypoxia Contribute to the Antifibrotic Effect of SGLT2 Inhibitor Dapagliflozin in the Diabetic Kidney
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 …
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Journal:
Authors:
- Hodrea J,
- Balogh DB,
- Hosszu A,
- Lenart L,
- Besztercei B,
- koszegi S,
- Sparding N,
- Genovese F,
- Wagner LJ,
- Szabo AJ,
- Fekete A,
Extracellular Matrix Research, Cardiovascular System
20. Mar 2020
Atrial Fibrillation and Cardiac Fibrosis: A Review on the Potential of Extracellular Matrix Proteins as Biomarkers
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…
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Journal:
Authors:
- Reese-Petersen AL,
- Olesen MS,
- Karsdal MA,
- Svendsen J,
- Genovese F,
Renal System, Chronic Renal Disease, Extracellular Matrix Research
14. Jan 2020
Imbalanced turnover of collagen type III is associated with disease progression and mortality in high-risk chronic kidney disease patients
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…
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Journal:
Authors:
- Genovese F,
- Rasmussen DGK,
- Karsdal M,
- Jesky M,
- Ferro C,
- Fenton A,
- Cockwell P,
Renal System, Chronic Renal Disease, Extracellular Matrix Research, Biomarker position
5. Nov 2019
Collagen turnover profiles in chronic kidney disease.
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…
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Journal:
Authors:
- Rasmussen DG,
- Boesby L,
- Nielsen SH,
- Teepel M,
- Birot S,
- Karsdal MA,
- Kamper Al,
- Genovese F,
Endocrinology, Type 1-Diabetes, Renal System, Cardiovascular System
13. Sep 2019
Markers of Collagen Formation and Degradation Reflect Renal Function and Predict Adverse Outcomes in Patients With Type 1 Diabetes.
OBJECTIVE:
Patients with type 1 diabetes (T1D) have a higher risk of developing chronic kidney disease, cardiovascular events (CVEs), and mortality than the general population. We hypothesized that two previously published biomarkers, namely PRO-C6, a biomarker of collagen type VI formation, and C3…
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Journal:
Authors:
- Pilemann-Lyberg S,
- Rasmussen DG,
- Hansen TW,
- Tofte N,
- Winther SA,
- Holm Nielsen S,
- Theilade S,
- Karsdal MA,
- Genovese F,
- Rossing P,
Cardiovascular System, Respiratory System
17. May 2019
Pressure overload induced right ventricular remodeling is not attenuated by the anti-fibrotic agent pirfenidone
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…
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Journal:
Authors:
- 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,
Extracellular Matrix Research, Respiratory System, Idiopathic Pulmonary Fibrosis, Lung, Chronic Obstructive Pulmonary Disease
12. Feb 2019
Serological Assessment of Activated Fibroblasts by alpha-Smooth Muscle Actin (α-SMA): A Noninvasive Biomarker of Activated Fibroblasts in Lung Disorders
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 …
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Journal:
Authors:
- Holm Nielsen S,
- Willumsen N,
- Leeming DJ,
- Daniels SJ,
- brix s,
- Karsdal MA,
- Genovese F,
- Nielsen MJ,
Renal System, Extracellular Matrix Research
7. Dec 2018
A non-invasive biomarker of type III collagen degradation reflects ischaemia reperfusion injury in rats.
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…
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Journal:
Authors:
- Rasmussen DG,
- Nielsen PM,
- Kasab-Oglo ôY,
- Nielsen SH,
- kerulf-Lassen C,
- Karsdal MA,
- Genovese F,
- Nørregaard R,
Cardiovascular System, Atherosclerosis
6. Nov 2018
Markers of Basement Membrane Remodeling Are Associated With Higher Mortality in Patients With Known Atherosclerosis.
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 assoc…
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Journal:
Authors:
- Nielsen SH,
- Tengryd C,
- Edsfeldt A,
- Brix S,
- Genovese F,
- Bengtsson E,
- Karsdal MA,
- Leeming DJ,
- Nilsson J,
- Goncalves I,
Renal System, Chronic Renal Disease, Extracellular Matrix Research
1. Oct 2018
A novel biomarker of laminin turnover is associated with disease progression and mortality in chronic kidney disease.
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 c…
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Journal:
Authors:
- Holm Nielsen S,
- guldager Kring Rasmussen D,
- Brix S,
- Jesky M,
- Fenton A,
- Ferro CJ,
- Karsdal MA,
- Genovese F,
- Cockwell P,
Cardiovascular System
11. Sep 2018
Cardiac magnetic resonance using late gadolinium enhancement and atrial T1 mapping predicts poor outcome in patients with atrial fibrillation after catheter ablation therapy
To determine the pre-procedural value of different fibrotic biomarkers and comprehensive cardiac magnetic resonance (CMR) for the prediction of poor response to ablation therapy in patients with atrial fibrillation (AF). Left atrial (LA) late gadolinium enhancement (LGE) and native LA T1 relaxation …
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Journal:
Authors:
- Luetkens JA,
- Wolpers AC,
- Beiert T,
- Kuetting D,
- Dabir D,
- Homsi R,
- Meemdermann H,
- Day'e NA,
- Knappe V,
- Karsdal MA,
- Nielsen SH,
- Genovese F,
- Stöckjgt F,
- Linhart M,
- Thomas D,
- Nickenig G,
- Schild HH,
- Schrickel JW,
- Andrié RP,
Cardiovascular System, Atherosclerosis, Extracellular Matrix Research, Biomarker position
28. Aug 2018
A biomarker of collagen type I degradation is associated with cardiovascular events and mortality in patients with atherosclerosis.
OBJECTIVE:
Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix (ECM) proteins in the arterial wall. Collagen type I (COL1), a component of the arterial ECM, is cleaved by matrix metalloproteinases (MMPs) and known to be remodelled in atherosclerosis. We explor…
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Journal:
Authors:
- Holm Nielsen S,
- Tengryd C,
- Edsfeldt A,
- Genovese F,
- Bengtsson E,
- Karsdal MA,
- Leeming DJ,
- Nilsson J,
- Goncalves I,
Type 2-Diabetes, Endocrinology, Extracellular Matrix Research
11. Apr 2018
Higher collagen VI formation is associated with all-cause mortality in type 2 diabetic patients with microalbuminuria
OBJECTIVE:
Type 2 diabetes is a common risk factor for the development of chronic kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has been associated with renal fibrosis and CKD. We investigated the hypothesis that PRO-C6, a product specifically generated during COL VI fo…
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Journal:
Authors:
- Rasmussen DGK,
- Hansen TW,
- von Scholten BJ,
- Nielsen SH,
- Reinhard H,
- Parving HH,
- Tepel M,
- Karsdal MA,
- Jacobsen PK,
- Genovese F,
- Rossing P,
Extracellular Matrix Research, Atherosclerosis
31. Mar 2018
Assessment of extracellular matrix-related biomarkers in patients with lower extremity artery disease
BACKGROUND:
The prevalence of lower extremity artery disease (LEAD) is high (20%-25%) in the population older than 65 years, but patients are seldom identified until the disease is advanced. Circulating markers of disease activity might provide patients with a key opportunity for timely treatment. …
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Journal:
Authors:
- Hernández-Aguilera A,
- Nielsen SH,
- Bonache C,
- Fernández-Arroyo S,
- Martín-Paredero V,
- Fibla M,
- Karsdal MA,
- Genovese F,
- Menendez JA,
- Camps J,
- Joven J,
Chronic Obstructive Pulmonary Disease, Idiopathic Pulmonary Fibrosis, Lung, Extracellular Matrix Research
7. Mar 2018
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…
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Journal:
Authors:
- Nielsen SH,
- Willumsen N,
- Brix S,
- Sun S,
- Manon-Jensen T,
- Karsdal MA,
- Genovese F,
Cardiovascular System, Extracellular Matrix Research, Myocardial Fibrosis
1. Jan 2018
Accelerated collagen turnover in women with angina pectoris without obstructive coronary artery disease: An iPOWER substudy
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 patie…
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Journal:
Authors:
- Nielsen SH,
- Mygind ND,
- Michelsen MM,
- Bechsgaard DF,
- Suhrs HE,
- Genovese F,
- Nielsen HB,
- Brix S,
- Karsdal MA,
- Prescott E,
- Kastrup J,
Cardiovascular System, Extracellular Matrix Research
14. Dec 2017
Understanding Cardiac Extracellular Matrix Remodeling to Develop Biomarkers of Myocardial Infarction Outcomes
Cardiovascular Disease (CVD) is the most common cause of death in industrialized countries, and myocardial infarction (MI) is a major CVD with significant morbidity and mortality. Following MI, the left ventricle (LV) undergoes a wound healing response to ischemia that results in extracellular matri…
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Journal:
Authors:
- Nielsen SH,
- Mouton AJ,
- DeLeon-Pennell KY,
- Genovese F,
- Karsdal MA,
- Lindsey ML,
Renal System, Chronic Renal Disease
11. Dec 2017
Urinary endotrophin predicts disease progression in patients with chronic kidney disease
Renal fibrosis is the central pathogenic process in progression of chronic kidney disease (CKD). Collagen type VI (COL VI) is upregulated in renal fibrosis. Endotrophin is released from COL VI and promotes pleiotropic pro-fibrotic effects. Kidney disease severity varies considerably and accurate inf…
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Journal:
Authors:
- Rasmussen DG,
- Fenton A,
- Jesky M,
- Ferro C,
- Boor P,
- Tepel M,
- Karsdal MA,
- Genovese F,
- Cockwell P,
Extracellular Matrix Research, Peripheral Vascular Disease
12. Aug 2017
Non-invasive evaluation of extracellular matrix remodeling in peripheral artery disease
AIM:
Peripheral artery disease (PAD) is a common manifestation of systemic atherosclerosis affecting peripheral arteries. The underlying pathology of PAD are disorganized extracellular matrix (ECM), caused by inflammation and oxidation. Previous studies have demonstrated an important structure dis…
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Journal:
Authors:
- Aguilera AH,
- Nielsen SH,
- Fernández-Arroyo S,
- Martín-Paredero V,
- Karsdal MA,
- Genovese F,
- Camps J,
- Joven J,
Renal System, Type 2-Diabetes, Obesity
26. Jul 2017
High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy
ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates …
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Journal:
Authors:
- Dower K,
- Zhao S,
- Schlerman FJ,
- Savary L,
- Campanholle G,
- Johnson BG,
- Xi L,
- Nguyen V,
- Zhan Y,
- Lech MP,
- Wang J,
- Nie Q,
- Karsdal MA,
- Genovese F,
- Boucher G,
- Brown TP,
- Zhang B,
- Homer BL,
- Martinez RV,
Renal System, Chronic Renal Disease
21. Apr 2017
Non-invasive quantification of collagen turnover in renal transplant recipients
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…
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Journal:
Authors:
- Stribos EGD,
- Nielsen SH,
- Brix S,
- Karsdal MA,
- Seelen MA,
- van Goor H,
- Bakker SJL,
- Olinga P,
- Mutsaers HAM,
- Genovese F,
Chronic Renal Disease, Renal System
12. Apr 2017
Serum endotrophin, a type VI collagen cleavage product, is associated with increased mortality in chronic kidney disease
BACKGROUND:
Patients with chronic kidney disease (CKD) are at increased risk of end-stage renal disease (ESRD) and early mortality. The underlying pathophysiological processes are not entirely understood but may include dysregulation of extracellular matrix formation with accelerated systemic and r…
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Journal:
Authors:
- Genovese F,
- Cockwell P,
- Karsdal MA,
- Sørensen J,
- Ferro CJ,
- Jesky MD,
- Fenton A,
Chronic Renal Disease
20. Mar 2017
Urinary collagen degradation products as early markers of progressive renal fibrosis
BACKGROUND:
Renal fibrogenesis is associated with increased ECM remodeling and release of collagen fragments in urine in progressive renal disease. We investigated the diagnostic value of urinary collagen degradation products in a proteinuria-driven fibrosis rat model with and without anti-fibrotic…
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Journal:
Authors:
- Hijmans RS,
- Rasmussen DG,
- Yazdani S,
- Navis G,
- van Goor H,
- Karsdal MA,
- Genovese F,
- van den Born J,
Chronic Obstructive Pulmonary Disease
11. Jan 2017
Development of a Novel Enzyme-Linked Immunosorbent Assay Targeting a Neo-Epitope Generated by Cathepsin-Mediated Turnover of Type III Collagen and Its Application in Chronic Obstructive Pulmonary Disease
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…
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Authors:
Type 2-Diabetes
8. Sep 2016
Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes
AIMS/HYPOTHESIS:
The treatment of type 2 diabetes with full peroxisome proliferator-activated receptor gamma (PPARγ) agonists improves insulin sensitivity, but is associated with weight gain, heart failure, peripheral oedema and bone loss. Endotrophin, the C-terminal fragment of the α3 chain of pro…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Genovese F,
- Leeming DJ,
- Nielsen MJ,
- Riis BJ,
- Christiansen C,
- Byrjalsen I,
- Schuppan D,
Respiratory System
1. Aug 2016
Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF
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 aberran…
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Journal:
Authors:
- 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,
Extracellular Matrix Research, Renal System
22. May 2016
Precision-Cut Kidney Slices as a Tool to Understand the Dynamics of Extracellular Matrix Remodeling in Renal Fibrosis
The aim of this study was to set up an ex vivo model for renal interstitial fibrosis in order to investigate the extracellular matrix (ECM) turnover profile in the fibrotic kidney. We induced kidney fibrosis in fourteen 12-week-old male Sprague Dawley rats by unilateral ureteral obstruction (UUO) su…
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Journal:
Authors:
- Genovese F,
- Kàrpàti ZS,
- Nielsen SH,
- Karsdal MA,
Renal System
1. Feb 2016
Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease
During chronic kidney disease (CKD) there is a dysregulation of extracellular matrix (ECM) homeostasis leading to renal fibrosis. Lysosomal proteases such as cathepsins (Cts) regulate this process in other organs, however, their role in CKD is still unknown. Here we describe a novel role for catheps…
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Journal:
Authors:
- Fox C,
- Cocchiaro P,
- Oakley F,
- Howarth R,
- Callaghan K,
- Leslie J,
- Luli S,
- Wood KM,
- Sheerin NS,
- Genovese F,
- Moles A,
Extracellular Matrix Research
21. Dec 2015
Protein degradation fragments as diagnostic and prognostic biomarkers of connective tissue diseases: understanding the extracellular matrix message and implication for current and future serological biomarkers
The aim of this review is to discuss the potential usefulness of novel biochemical markers of connective tissues: neo-epitopes of extracellular matrix proteins generated by post-translational modifications by tissue proteinases. As each modification results from a specific local physiological or pat…
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Authors:
Extracellular Matrix Research
22. Aug 2015
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…
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Journal:
Authors:
- Karsdal MA,
- Genovese F,
- Madsen EA,
- Manon-Jensen T,
- Schuppan D,
Renal System, Chronic Renal Disease
1. Jul 2015
Serum and urine markers of collagen degradation reflect renal fibrosis in experimental kidney diseases
BACKGROUND:
The extent of renal fibrosis in chronic kidney disease (CKD) is the best predictor for progression of most renal diseases. To date, no established biomarkers of renal fibrosis exist.
METHODS:
We measured circulating and urinary-specific matrix metalloproteinase (MMP)-generated colla…
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Journal:
Authors:
- Papasotiriou M,
- Genovese F,
- Klinkhammer BM,
- Kunter U,
- Nielsen SH,
- Karsdal MA,
- Floege J,
- Boor P,
Hepatic System, Non-Alcoholic Fatty Liver Disease
15. May 2015
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…
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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,
Extracellular Matrix Research, Renal System, Chronic Renal Disease
26. Apr 2015
Turnover of type III collagen reflects disease severity and is associated with progression and microinflammation in patients with IgA nephropathy
BACKGROUND:
Renal fibrosis is the hallmark of progression to end-stage kidney disease. Non-invasive biomarkers of renal fibrosis could serve as specific end points in clinical trials and improve monitoring and stratification of patients with chronic kidney disease (CKD). To address this, we measure…
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Journal:
Authors:
- Genovese F,
- Boor P,
- Papasotiriou M,
- Leeming DJ,
- Karsdal MA,
- Floege J,
Extracellular Matrix Research
1. Apr 2015
The importance of extracellular matrix for cell function and in vivo likeness
OBJECTIVE:
Fibrotic diseases may be described as a disease of the extracellular matrix, where the balance between matrix formation and degradation has been shifted leading to an accumulation of matrix. Currently a fit for purpose model and readily available approach are adapted when doing cell cult…
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Journal:
Authors:
- Hansen NU,
- Genovese F,
- Leeming DJ,
- Karsdal MA,
Rheumatology, Alkaptonuria
1. Mar 2015
Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy
Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-…
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Journal:
Authors:
- Nemethova M,
- Radvanszky J,
- Kadasi L,
- Ascher DB,
- Pires DE,
- Blundell TL,
- Porfirio B,
- Mannoni A,
- Santucci A,
- Milucci L,
- Sestini S,
- , Biolcati G,
- Sorge,
- Aurizi C,
- Aquaron R,
- Alsbou M,
- Marques Lourenço C,
- Ramadevi K,
- Ranganath LR,
- Gallagher JA,
- van Kan C,
- Hall AK,
- Olsson B,
- Ayoob H,
- Timmis OG,
- Le Quan Sang KH,
- Genovese F,
- Imrich R,
- Rovensky J,
- Srinivasaraghavan R,
- Bharadwaj SK,
- Spiegel R,
- Zatkova A,
Rheumatology, Gout
1. Jan 2015
Investigating the Robustness and Diagnostic Potential of Extracellular Matrix Remodelling Biomarkers in Alkaptonuria
BACKGROUND AND AIM:
Alkaptonuria (AKU) clinical manifestations resemble severe arthritis. The Suitability of Nitisinone in Alkaptonuria 1 (SONIA 1) study is a dose-finding trial for nitisinone treatment of AKU patients. We tested a panel of serum and urinary biomarkers reflecting extracellular matr…
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Journal:
Authors:
- Genovese F,
- Siebuhr AS,
- Musa K,
- Gallagher JA,
- Milan AM,
- Karsdal MA,
- Rovensky J,
- Bay-Jensen AC,
- Ranganath LR,
Rheumatology, Osteoarthritis
4. Dec 2014
Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment
BACKGROUND:
Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied.
METHOD…
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Journal:
Authors:
- Ranganath LR,
- Milan AM,
- Hughes AT,
- Dutton JJ,
- Fitzgerald R,
- Briggs MC,
- Bygott H,
- Psarelli EE,
- Cox TF,
- Gallagher JA,
- Jarvis JC,
- van Kan C,
- Hall AK,
- Laan D,
- Olsson B,
- Szamosi J,
- Rudebeck M,
- Kullenberg T,
- Cronlund A,
- Svensson L,
- Junestrand C,
- Ayoob H,
- Timmis OG,
- Sireau N,
- Le Quan Sang KH,
- Genovese F,
- Braconi D,
- Santucci A,
- Nemethova M,
- Zatkova A,
- McCaffrey J,
- Christensen P,
- Ross G,
- Imrich R,
- Rovensky J,
Renal System, Extracellular Matrix Research
29. Oct 2014
Association of versican turnover with all-cause mortality in patients on haemodialysis
OBJECTIVE:
Cardiovascular diseases are among the most common causes of mortality in renal failure patients undergoing haemodialysis. A high turnover rate of the proteoglycan versican, represented by the increased presence of its fragmentation products in plasma, has previously been associated with …
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Journal:
Authors:
- Genovese F,
- Karsdal MA,
- Leeming DJ,
- Scholze A,
- Tepel M,
Respiratory System, Extracellular Matrix Research
29. Oct 2014
The role of extracellular matrix quality in pulmonary fibrosis
This review discusses the role of extracellular matrix (ECM) quality in the pathogenesis of pulmonary fibrosis (PF). In PF, the highly ordered structure of collagens and elastin within the ECM of the lung is severely disrupted and lacks its original tissue quality. Discussions about the ECM have foc…
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Journal:
Authors:
- Kristensen JH,
- Karsdal MA,
- Genovese F,
- Johnson S,
- Svensson B,
- Jacobsen S,
- Hägglund P,
- Leeming DJ,
Renal System, Extracellular Matrix Research
28. Mar 2014
The extracellular matrix in the kidney: a source of novel non-invasive biomarkers of kidney fibrosis?
Interstitial fibrosis is the common endpoint of end-stage chronic kidney disease (CKD) leading to kidney failure. The clinical course of many renal diseases, and thereby of CKD, is highly variable. One of the major challenges in deciding which treatment approach is best suited for a patient but also…
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Journal:
Authors:
- Genovese F,
- Manresa AA,
- Leeming DJ,
- Karsdal MA,
- Boor P,
Extracellular Matrix Research, Cardiovascular System, Atherosclerosis
3. Jun 2013
A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease
Extracellular matrix remodelling is a prerequisite for plaque rupture in atherosclerotic lesion. Versican, an extracellular matrix proteoglycan present in normal and atherosclerotic arteries is a substrate for matrix metalloproteinases (MMPs) present in macrophage rich areas. The aim of the current …
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Journal:
Authors:
- Barascuk N,
- Genovese F,
- Larsen L,
- Byrjalsen I,
- Zheng Q,
- Sun S,
- Hosbond S,
- Poulsen TS,
- Diederichsen A,
- Jensen JM,
- Mickley H,
- Register TC,
- Rasmussen LM,
- Leeming DJ,
- Christiansen C,
- Karsdal MA,
Extracellular Matrix Research, Hepatic System
15. May 2013
Biglycan fragmentation in pathologies associated with extracellular matrix remodeling by matrix metalloproteinases
BACKGROUND:
The proteoglycan biglycan (BGN) is involved in collagen fibril assembly and its fragmentation is likely to be associated with collagen turnover during the pathogenesis of diseases which involve dysregulated extracellular matrix remodeling (ECMR), such as rheumatoid arthritis (RA) and li…
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Journal:
Authors:
- Genovese F,
- Barascuk N,
- Larsen L,
- Nawrocki A,
- Li Y,
- Zheng Q,
- Wang J,
- Veidal SS,
- Leeming DJ,
- Karsdal MA,
Extracellular Matrix Research
11. Mar 2013
Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure
Increased attention is paid to the structural components of tissues. These components are mostly collagens and various proteoglycans. Emerging evidence suggests that altered components and noncoded modifications of the matrix may be both initiators and drivers of disease, exemplified by excessive ti…
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Journal:
Authors:
- Karsdal MA,
- Nielsen MJ,
- Sand JM,
- Henriksen K,
- Genovese F,
- Bay-Jensen AC,
- Adamkewicz JI,
- Christiansen C,
- Leeming DJ,
Respiratory System, Chronic Obstructive Pulmonary Disease, Idiopathic Pulmonary Fibrosis
11. Jul 2012
Serological investigation of the collagen degradation profile of patients with chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis
In both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), abnormally high collagen remodeling occurs within the lung tissue. Matrix metalloproteinase (MMP)-degraded type I, III, IV, V and VI collagen and a disintegrin and metalloproteinase with thrombospondin moti…
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Journal:
Authors:
- Leeming DJ,
- Sand JM,
- Nielsen MJ,
- Genovese F,
- Martinez FJ,
- Hogaboam CM,
- Han MK,
- Klickstein LB,
- Karsdal MA,
Extracellular Matrix Research, Cardiovascular System, Acute Myocardial Infarct
6. Jul 2012
Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker
BACKGROUND:
Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical s…
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Journal:
Authors:
- Vassiliadis E,
- Rasmussen LM,
- Byrjalsen I,
- Larsen DV,
- Chaturvedi R,
- Hosbond S,
- Saabye L,
- Diederichsen AC,
- Genovese F,
- Duffin KL,
- Zheng Q,
- Chen X,
- Leeming DJ,
- Christiansen C,
- Karsdal MA,
Hepatic System, Extracellular Matrix Research
3. Jan 2012
Molecular serum markers of liver fibrosis
Fibrosis is a hallmark histologic event of chronic liver diseases and is characterized by the excessive accumulation and reorganization of the extracellular matrix (ECM). The gold standard for assessment of fibrosis is liver biopsy. As this procedure has various limitations, including risk of patien…
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Journal:
Authors:
- Liu T,
- Wang X,
- Karsdal MA,
- Leeming DJ,
- Genovese F,