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Increased turnover of extracellular matrix proteins is seen in many different diseases and is an underlying and driving feature of pathogenesis. An increased ratio of formation over degradation of extracellular matrix proteins, such as collagens, leads to accumulation of proteins in the tissues, ult...

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Objectives: There is a need for precision medicine and an unspoken promise of an optimal approach for identification of the right patients for value-based medicine based on big data. However, there may be a misconception that measurement of proteins is more valuable than measurement of fewer selecte...

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Abstract Abdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemi...

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Background: Rupture of atherosclerotic plaques is the major cause of acute cardiovascular events. The biomarker PRO-C6 measuring Endotrophin, a matrikine of collagen type VI, may provide valuable information detecting subjects in need of intensified strategies for secondary prevention. Objective: I...

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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...

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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...

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Pulmonary fibrosis has been identified as a main factor leading to pulmonary dysfunction and poor quality of life in post-recovery Severe Acute Respiratory Syndrome (SARS) survivor's consequent to SARS-Cov-2 infection. Thus there is an urgent medical need for identification of readily available biom...

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Background and aims: A vulnerable plaque is an atherosclerotic plaque that is rupture-prone with a higher risk to cause cardiovascular symptoms such as myocardial infarction or stroke. Mimecan or osteoglycin is a small leucine-rich proteoglycan, important for collagen fibrillogenesis, that has been ...

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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...

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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...

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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 ...

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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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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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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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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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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...

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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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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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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...

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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...

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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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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...

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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...

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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...

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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...

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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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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...

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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...

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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...

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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...

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