he PRO-C6 assay, a reflection of collagen type VI synthesis, has been proposed as a non-invasive early biomarker of kidney fibrosis. We aimed to investigate cross-sectional and longitudinal associations between plasma and urine PRO-C6 and proven histological changes after kidney transplantation. The...
October 7, 2020
Journal:
J Clin Med
Author:
Yepes-Calderón M, Sotomayor CG, Rasmussen DGK, Hijmans RS, Te Velde-Keyzer CA, van Londen M, van Dijk M, Diepstra A, Berger SP, Karsdal MA, Bemelman FJ, de Fijter JW, Kers J, Florquin S, Genovese F, Bakker SJL, Sanders JS, Van Den Born J
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
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...
May 1, 2020
Journal:
J Intern Med
Author:
Nielsen SH, Jonasson L, Kalogeropoulos K, Karsdal MA, Reese-Petersen AL, Auf dem Keller U, Genovese F, Nilsson J, Goncalves I
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...
April 3, 2020
Journal:
Sci Rep
Author:
Nielsen SH, Mortensen JH, Willumsen N, guldager Kring Rasmussen D, Mogensen DJ, Di Sabatino A, Mazza G, Jørgensen LN, giuffrida P, Pinzani M, Klinge LG, Kjeldsen J, Leeming DJ, Karsdal MA, Genovese F
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, Koszeqi S, Sparding N, Genovese F, Wagner LJ, Szabo AJ, Fekete A
Background\r\nTubulointerstitial 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...
January 14, 2020
Journal:
ERA-EDTA Clinical Kidney Journal
Author:
Genovese F, Rasmussen DGK, Karsdal M, Jesky M, Ferro C, Fenton A, Cockwell P
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:
Rasmussen DG, Boesby L, Nielsen SH, Teepel M, Birot S, Karsdal MA, Kamper Al, Genovese F
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 C3M...
September 13, 2019
Journal:
Diabetes Care
Author:
Pilemann-Lyberg S, Rasmussen DG, Hansen TW, Tofte N, Winther SA, Holm Nielsen S, Theilade S, Karsdal MA, Genovese F, Rossing P
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:
Rasmussen DG, Nielsen PM, Kasab-Oglo ôY, Nielsen SH, Kerulf-Lassen C, Karsdal MA, Genovese F, Nørregaard R
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
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
KEY POINTS: Increased activation of the renin-angiotensin-aldosterone system (RAAS) and elevated growth factor production are of crucial importance in the development of renal fibrosis leading to diabetic kidney disease. The aim of this study was to provide evidence for the antifibrotic potential of...
January 17, 2019
Journal:
Am J Physiol Endocrinol Metab
Author:
koszegi S, Molnar A, Lenart L, Hodrea J, Balogh DB, Lakat T, Szkibinszjik J, Hoszu A, Sparding N, Genovese F, Wagner L, Vannay A, Szabo AJ, Fekete A
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, guldager Kring Rasmussen D, Brix S, Jesky M, Fenton A, Ferro CJ, Karsdal MA, Genovese F, Cockwell P
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 ...
September 11, 2018
Journal:
Sci Rep
Author:
Luetkens JA, Wolpers AC, Beiert T, Kuetting D, Dabir D, Homsi R, Meemdermann H, Day NA, Knappe V, Karsdal MA, Nielsen SH, Genovese F, Stöckjgt F, Linhart M, Thomas D, Nickenig G, Schild HH, Schrickel JW, Andrié RP
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 explore...
August 28, 2018
Journal:
J Intern Med
Author:
Holm Nielsen S, Tengryd C, Edsfeldt A, Genovese F, Bengtsson E, Karsdal MA, Leeming DJ, Nilsson J, Goncalves I
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, Nielsen HB, Brix S, Karsdal MA, Prescott E, Kastrup J
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 for...
April 11, 2018
Journal:
Diabetes Care
Author:
Rasmussen DGK, Hansen TW, von Scholten BJ, Nielsen SH, Reinhard H, Parving HH, Tepel M, Karsdal MA, Jacobsen PK, Genovese F, Rossing P
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. W...
March 31, 2018
Journal:
J Vasc Surg
Author:
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
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
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...
December 14, 2017
Journal:
Matrix Biol
Author:
Nielsen SH, Mouton AJ, DeLeon-Pennell KY, Genovese F, Karsdal MA, Lindsey ML
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...
December 1, 2017
Journal:
Scientific Reports, Nature
Author:
Rasmussen DG, Fenton A, Jesky M, Ferro C, Boor P, Tepel M, Karsdal MA, Genovese F, Cockwell P
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 disor...
August 12, 2017
Journal:
Atherosclerosis
Author:
Aguilera AH, Nielsen SH, Fernández-Arroyo S, Martín-Paredero V, Karsdal MA, Genovese F, Camps J, Joven J
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 ...
July 26, 2017
Journal:
PLoS One
Author:
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
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
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 re...
April 12, 2017
Journal:
PLoS One
Author:
Genovese F, Cockwell P, Karsdal MA, Sørensen J, Ferro CJ, Jesky MD, Fenton A
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 re...
March 20, 2017
Journal:
J Transl Med.
Author:
Hijmans RS, Rasmussen DG, Yazdani S, Navis G, van Goor H, Karsdal MA, Genovese F, van den Born J
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...
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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