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Cited by 644Cardiac Fibrosis and RemodelingCardiovascular Function and Risk FactorsHeart Failure Treatment and Management

The DOI matches its Crossref record; 54 of the 55 references it cites were found in a registry or an index.

Cardiac Inflammation Contributes to Changes in the Extracellular Matrix in Patients With Heart Failure and Normal Ejection Fraction

Westermann, Dirk, Lindner, Diana, Kasner, Mario, Zietsch, Christine, Savvatis, K., Escher, F., von Schlippenbach, J., Skurk, C., Steendijk, Paul, Riad, Alexander, Poller, Wolfgang, Schultheiss, Heinz-Peter, Tschöpe, Carsten·2011·Circulation Heart Failure
DOI 10.1161/circheartfailure.109.931451
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Abstract

BACKGROUND: The pathophysiology of heart failure with normal ejection fraction (HFNEF) is still under discussion. Here we report the influence of cardiac inflammation on extracellular matrix (ECM) remodeling in patients with HFNEF. METHODS AND RESULTS: We investigated left ventricular systolic and diastolic function in 20 patients with HFNEF and 8 control patients by conductance catheter methods and echocardiography. Endomyocardial biopsy samples were also obtained, and ECM proteins as well as cardiac inflammatory cells were investigated. Primary human cardiac fibroblasts were outgrown from the endomyocardial biopsy samples to investigate the gene expression of ECM proteins after stimulation with transforming growth factor-β. Diastolic dysfunction was present in the HFNEF patients compared with the control patients. In endomyocardial biopsy samples from HFNEF patients, we found an accumulation of cardiac collagen, which was accompanied by a decrease in the major collagenase system (matrix metalloproteinase-1) in the heart. Moreover, a subset of inflammatory cells, which expressed the profibrotic growth factor transforming growth factor-β, could be documented in the HFNEF patients. Stimulation of primary human cardiac fibroblasts from HFNEF patients with transforming growth factor-β resulted in transdifferentiation of fibroblasts to myofibroblasts, which produced more collagen and decreased the amount of matrix metalloproteinase-1, the major collagenase in the human heart. A positive correlation between cardiac collagen, as well as the amount of inflammatory cells, and diastolic dysfunction was evident and suggests a direct influence of inflammation on fibrosis triggering diastolic dysfunction. CONCLUSIONS: Cardiac inflammation contributes to diastolic dysfunction in HFNEF by triggering the accumulation of ECM.

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Crossref · 10.1161/circheartfailure.109.931451

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Metadata

Authors
Westermann, D., Lindner, D., Kasner, M., Zietsch, C., Savvatis, K., Escher, F., von Schlippenbach, J., Skurk, C., Steendijk, P., Riad, A., Poller, W., Schultheiss, H.-P., & Tschöpe, C.
Affiliations
  • Leiden University Medical Center (NL)
  • From the Department of Cardiology and Pneumology (D.W., D.L., M.K., C.Z., K.S., F.E., J.v.S., C.S., A.R., W.P., H.-P.S., C.T.), Charité, Universititäts-Medizin Berlin, Campus Benjamin Franklin, Berlin, Germany, and Department of Cardiology (P.S.), Leiden University Medical Center, Leiden, The Netherlands.
ORCID
Venue
Circulation Heart Failure
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2011-01
Volume
4
Issue
1
Pages
44-52
ISSN
  • 1941-3289 (ISSN-L)
  • 1941-3297
DOI
10.1161/circheartfailure.109.931451
OpenAlex
W2131184290
Cited by
644
References
55
Citations by year
2026: 32 · 2025: 48 · 2024: 53 · 2023: 50 · 2022: 57 · 2021: 58 · 2020: 49 · 2019: 37 · 2018: 45 · 2017: 49 · 2016: 35 · 2015: 42 · 2014: 30 · 2013: 21 · 2012: 17
FWCI
12.97
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation Heart Failure (publishedVersion)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
Keywords
heart failure with preserved ejection fraction, cardiac inflammation, extracellular matrix remodeling, diastolic dysfunction, myocardial fibrosis, collagen deposition, MMP-1, TGF-beta, myofibroblasts, endomyocardial biopsy, left ventricular systolic function
MeSH terms
Adult, Aged, Biopsy, Cells, Cultured, Collagen, Extracellular Matrix, Female, Fibroblasts, Fibrosis, Heart, Heart Failure, Humans, Inflammation, Male, Middle Aged, Myocardium, Stroke Volume, Case-Control Studies, Transforming Growth Factor beta, Ventricular Function, Left, Extracellular Matrix Proteins, Disease Progression, Matrix Metalloproteinase 1

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