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A biomarker of collagen type I degradation is associated with cardiovascular events and mortality in patients with atherosclerosis.

January 1, 2019

J Intern Med

Abstract 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 explored whether the MMP-mediated COL1 biomarker, C1M, was associated with cardiovascular events, […]

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Assessment of liver fibrosis progression and regression by a serological collagen turnover profile.

January 1, 2019

Am J Physiol Gastrointest Liver Physiol

Abstract There is a need for noninvasive biomarkers that can identify patients with progressive liver fibrosis and monitor response to antifibrotic therapy. An equally important need is identification of patients with spontaneous fibrosis regression, since they may not need treatment nor be included in clinical studies with fibrosis as end point. Circulating biomarkers, originating from […]

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RAAS inhibitors directly reduce diabetes-induced renal fibrosis via growth factor inhibition.

January 1, 2019

J Physiol

Abstract 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 RAAS inhibitor (RAASi) treatment and to explore the exact mechanism of […]

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Molecular taxonomy of osteoarthritis for patient stratification, disease management and drug development: biochemical markers associated with emerging clinical phenotypes and molecular endotypes.

January 1, 2019

Curr Opin Rheumatol

Abstract PURPOSE OF REVIEW This review focuses on the molecular taxonomy of osteoarthritis from the perspective of molecular biomarkers. We discuss how wet biochemical markers may be used to understand disease pathogenesis and progression and define molecular endotypes of osteoarthritis and how these correspond to clinical phenotypes. RECENT FINDINGS Emerging evidence suggests that osteoarthritis is […]

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IL-37 diminishes proteoglycan loss in human OA cartilage: donor-specific link between IL-37 and MMP-3.

January 1, 2019

Osteoarthritis Cartilage

Abstract OBJECTIVE A hallmark of osteoarthritis (OA) is degradation of articular cartilage proteoglycans. In isolated human OA chondrocytes, the anti-inflammatory cytokine Interleukin-37 (IL-37) lowers the expression of the proteolytic MMP and ADAMTS enzymes, which mediate this degradation. Therefore, we investigated if IL-37 protects against proteoglycan loss in freshly obtained human OA explants. MATERIAL AND METHODS […]

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Non-invasive biomarkers derived from the extracellular matrix associate with response to immune checkpoint blockade (anti-CTLA-4) in metastatic melanoma patients.

December 19, 2018

J Immunother Cancer

Abstract BACKGROUND Excessive extracellular matrix (ECM) remodeling and a reactive stroma can affect T-cell infiltration and T-cell activity in the tumor and hereby influence response to immune checkpoint inhibitors (ICI). In the pursuit of finding biomarkers that predict treatment response, we evaluated the association between serum biomarkers of collagen and vimentin turnover and outcomes in […]

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High turnover of extracellular matrix reflected by specific protein fragments measured in serum is associated with poor outcomes in two metastatic breast cancer cohorts.

December 1, 2018

Int J Cancer

Abstract Increased extracellular matrix (ECM) formation and matrix metalloprotease (MMP)-mediated ECM degradation are parts of tumorgenesis and generates collagen fragments that are released into circulation. We evaluated the association of specific collagen fragments measured in serum with outcomes in two independent metastatic breast cancer (MBC) cohorts. ELISAs were used to measure C1M (MMP-generated type I […]

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Markers of Basement Membrane Remodeling Are Associated With Higher Mortality in Patients With Known Atherosclerosis.

November 6, 2018

J Am Heart Assoc

Abstract 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 associated with clinical outcomes in patients with atherosclerosis. Methods and Results Neoepitope fragments of […]

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A Novel High Sensitivity Type II Collagen Blood-Based Biomarker, PRO-C2, for Assessment of Cartilage Formation.

November 6, 2018

Int J Mol Sci

Abstract N-terminal propeptide of type II collagen (PIINP) is a biomarker reflecting cartilage formation. PIINP exists in two main splice variants termed as type IIA and type IIB collagen NH₂-propeptide (PIIANP, PIIBNP). PIIANP has been widely recognized as a cartilage formation biomarker. However, the utility of PIIBNP as a marker in preclinical and clinical settings […]

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Assessment of extracellular matrix-related biomarkers in patients with lower extremity artery disease.

October 1, 2018

J Vasc Surg

Abstract 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. We tested the hypothesis that measuring blood-specific fragments generated during degradation […]

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