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…
Journal:
Authors:
- Nielsen SH,
- Jonasson L,
- Kalogeropoulos K,
- Karsdal MA,
- Reese-Petersen AL,
- Auf dem Keller U,
- Genovese F,
- Nilsson J,
- Goncalves I,
Collagen Biology and Non-Invasive Biomarkers of Liver Fibrosis
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…
Journal:
Authors:
- Karsdal MA,
- Daniels SJ,
- Nielsen SH,
- Bager C,
- Rasmussen DGK,
- Loomba R,
- Surabattula R,
- Villesen IF,
- Luo Y,
- Shevell D,
- Gudmann NS,
- Nielsen MJ,
- George J,
- Christian R,
- Leeming DJ,
- Schuppan D,
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…
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,
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…
Journal:
Authors:
- Rasmussen DG,
- Boesby L,
- Nielsen SH,
- Teepel M,
- Birot S,
- Karsdal MA,
- Kamper Al,
- Genovese F,
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…
Journal:
Authors:
- Rasmussen DG,
- Nielsen PM,
- Kasab-Oglo ôY,
- Nielsen SH,
- kerulf-Lassen C,
- Karsdal MA,
- Genovese F,
- Nørregaard R,
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…
Journal:
Authors:
- Nielsen SH,
- Tengryd C,
- Edsfeldt A,
- Brix S,
- Genovese F,
- Bengtsson E,
- Karsdal MA,
- Leeming DJ,
- Nilsson J,
- Goncalves I,
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 …
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,
Assessment of liver fibrosis progresion and regression by a serological collagen turnover profile
OBJECTIVE:
There is a need for non-invasive biomarkers that can identify patients with progressive liver fibrosis and monitor response to anti-fibrotic therapy. An equally important need is identification of patients with spontaneous fibrosis regression, since they may not need treatment nor be inc…
Authors:
- Karsdal MA,
- Hjuler ST,
- Luo Y,
- Rasmussen DG,
- Nielsen MJ,
- Nielsen SH,
- Leeming DJ,
- Goodman ZD,
- Arch RH,
- Patel K,
- Schuppan D,
Serum type XVI collagen is associated with colorectal cancer and ulcerative colitis indicating a pathological role in gastrointestinal disorders
Altered extracellular matrix (ECM) remodeling is an important part of the pathology of gastrointestinal (GI) disorders. In the intestine, type XVI collagen (col-16) plays a role in pathogenesis by affecting ECM architecture and induce cell invasion. Measuring col-16 in serum may therefore have bioma…
Journal:
Authors:
- Jensen C,
- Nielsen SH,
- Mortensen JH,
- Kjeldsen J,
- Klinge LG,
- Harling H,
- Jørgensen LN,
- Karsdal MA,
- Willumsen N,
- Leeming DJ,
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…
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,
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. …
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,
Matrix Metalloproteinase Mediated Type I Collagen Degradation is an Independent Predictor of Increased Risk of Acute Myocardial Infarction in Postmenopausal Women
Chronic fibro-proliferative diseases are associated with nearly 45% of all deaths in the developed world. Matrix metalloproteinase (MMP) mediated remodeling of the extracellular matrix (ECM) plays an important role in disease development. Degradation of type I collagen is considered having a major r…
Journal:
Authors:
- Bertelsen DM,
- Neergaard JS,
- Bager CL,
- Nielsen SH,
- Secher NH,
- Svendsen JH,
- Bihlet AR,
- Andersen JR,
- Karsdal MA,
- Christiansen C,
- Nielsen HB,
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,
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…
Journal:
Authors:
- Nielsen SH,
- Mygind ND,
- Michelsen MM,
- Bechsgaard DF,
- Suhrs HE,
- Genovese F,
- Nielsen HB,
- Brix S,
- Karsdal MA,
- Prescott E,
- Kastrup J,
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…
Journal:
Authors:
- Nielsen SH,
- Mouton AJ,
- DeLeon-Pennell KY,
- Genovese F,
- Karsdal MA,
- Lindsey ML,
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…
Journal:
Authors:
- Aguilera AH,
- Nielsen SH,
- Fernández-Arroyo S,
- Martín-Paredero V,
- Karsdal MA,
- Genovese F,
- Camps J,
- Joven J,
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,
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…
Journal:
Authors:
- Stribos EGD,
- Nielsen SH,
- Brix S,
- Karsdal MA,
- Seelen MA,
- van Goor H,
- Bakker SJL,
- Olinga P,
- Mutsaers HAM,
- Genovese F,
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…
Journal:
Authors:
- Genovese F,
- Kàrpàti ZS,
- Nielsen SH,
- Karsdal MA,
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…
Journal:
Authors:
- Papasotiriou M,
- Genovese F,
- Klinkhammer BM,
- Kunter U,
- Nielsen SH,
- Karsdal MA,
- Floege J,
- Boor P,