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Updated: Jul 3, 2026

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
Published on: June 14, 2016
Extracellular matrix turnover and inflammatory markers independently predict functional status and outcome in chronic
Anca Radauceanu1, Camille Ducki, Jean-Marc Virion
1Centre d'Investigation Clinique 9501, INSERM, Dommartin-lès-Toul, France.
Insights
Markers of extracellular matrix (ECM) remodeling, specifically amino-terminal propeptide of collagen III (PIIINP) and matrix metalloproteinase 1 (MMP-1), predict functional capacity and outcomes in chronic heart failure (CHF) patients. These findings highlight ECM turnover
Area of Science:
- Cardiology
- Biomarker Research
- Heart Failure Pathophysiology
Background:
- Inflammatory pathways are implicated in extracellular matrix (ECM) remodeling and chronic heart failure (CHF) progression.
- The interplay between inflammation, ECM remodeling markers, and CHF patient outcomes requires further investigation in large cohorts.
Purpose of the Study:
- To examine the relationship between serum markers of inflammation and ECM remodeling.
- To determine the influence of these markers on functional status and clinical outcomes in CHF patients.
Main Methods:
- Serum levels of ECM markers (PIIINP, MMP-1, TIMP-1) and inflammatory markers (hsCRP, IL-18, IL-10) were measured in 1009 CHF patients from the RECOVER trial.
- Correlations between marker classes were analyzed.
- Multivariable models assessed independent predictors of the 6-minute walk test (6-MWT) and CHF-related mortality/hospitalization.
Main Results:
- Positive correlations were observed between ECM remodeling markers and inflammatory markers.
- Amino-terminal propeptide of collagen III (PIIINP) and matrix metalloproteinase 1 (MMP-1) independently predicted 6-MWT performance.
- PIIINP was the sole independent predictor of death and CHF hospitalization.
Conclusions:
- Excessive ECM turnover, indicated by elevated PIIINP and MMP-1, is associated with reduced functional capacity in CHF.
- PIIINP is a significant independent predictor of adverse clinical outcomes, including mortality and hospitalization, in CHF patients.
Background:
Inflammatory pathways may promote extracellular matrix (ECM) remodeling and chronic heart failure (CHF) progression. The relationship between markers of inflammation and of ECM remodeling, and their influence on functional status and outcomes has not been examined in a large cohort of CHF patients.
Methods And Results:
We measured baseline blood serum collagen (amino-terminal propeptide of collagen III [PIIINP], metalloproteinase 1 [MMP-1], tissue inhibitor of metalloproteinase 1 [TIMP-1]), and inflammatory (high-sensitivity C-reactive protein [(hsCRP], interleukin [IL]-18, IL-10) markers in 1009 patients enrolled in the Research into Etanercept Cytokine Antagonism in Ventricular Dysfunction (RECOVER) trial. A positive correlation was detected between the 2 classes of markers (PIIINP to IL-18, MMP-1 and TIMP-1 to CRP, TIMP-1 to IL-18, MMP-1 to IL-10). In the adjusted multivariable model including all biomarkers, only PIIINP (P = .03) and MMP-1 (P = .048) were independent predictors of 6-minute walk test (6-MWT), whereas in another model including only inflammatory biomarkers, IL-18 was an independent predictor. PIIINP (P = .001) was the only biomarker independently associated with death and CHF hospitalization.
Conclusions:
The independent associations of PIIINP and MMP-1 with 6-MWT and PIIINP with CHF morbi-mortality suggest that excessive ECM turnover may be associated with functional capacity deterioration and poor outcome.
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