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Cardiac Inflammation Contributes to Changes in the Extracellular Matrix in Patients With Heart Failure and Normal Ejection Fraction
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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“The last two alterations are likely triggered by microvascular endothelial inflammation [70].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [70]
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Cites
Trends in Prevalence and Outcome of Heart Failure with Preserved Ejection Fraction
Owan, T., Hodge, D. O., Herges, R. M., Jacobsen, S. J., Roger, V. L., & Redfield, M. M. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052256 · Cited by 4,209
Paulus, W. J., Tschöpe, C., Sanderson, J. E., Rusconi, C., Flachskampf, F. A., Rademakers, F. E., Marino, P. N., Smiseth, O. A., Keulenaer, G. W. D., Leite-Moreira, A. F., et al. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehm037 · Cited by 2,646
Self-citationOutcome of Heart Failure with Preserved Ejection Fraction in a Population-Based Study
Bhatia, R. S., Tu, J. V., Lee, D. S., Austin, P. C., Fang, J., Haouzi, A., Gong, Y., & Liu, P. P. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa051530 · Cited by 1,959
Zile, M. R., Baicu, C. F., & Gaasch, W. H. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa032566 · Cited by 1,577
New Concepts in Diastolic Dysfunction and Diastolic Heart Failure: Part I
Zile, M. R., & Brutsaert, D. L. (2002) · Circulation · doi:10.1161/hc1102.105289 · Cited by 1,185
Spinale, F. G. (2007) · Physiological Reviews · doi:10.1152/physrev.00012.2007 · Cited by 1,139
Souders, C. A., Bowers, S., & Baudino, T. A. (2009) · Circulation Research · doi:10.1161/circresaha.109.209809 · Cited by 1,018
Spinale, F. G. (2002) · Circulation Research · doi:10.1161/01.res.0000013290.12884.a3 · Cited by 735
van Heerebeek, L., Hamdani, N., Handoko, M. L., Falcao-Pires, I., Musters, R. J., Kupreishvili, K., Ijsselmuiden, A. J. J., Schalkwijk, C. G., Bronzwaer, J. G. F., Diamant, M., et al. (2008) · Circulation · doi:10.1161/circulationaha.107.728550 · Cited by 723
Borlaug, B. A., Melenovsky, V., Russell, S. D., Kessler, K., Pacak, K., Becker, L. C., & Kass, D. A. (2006) · Circulation · doi:10.1161/circulationaha.106.632745 · Cited by 699
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van Heerebeek, L., Borbély, A., Niessen, H. W. M., Bronzwaer, J. G. F., van der Velden, J., Stienen, G. J. M., Linke, W. A., Laarman, G. J., & Paulus, W. J. (2006) · Circulation · doi:10.1161/circulationaha.105.587519 · Cited by 655
Kašner, M., Westermann, D., Paul Steendijk, A., Gaub, R., Wilkenshoff, U. M., Weitmann, K., Hoffmann, W. U., Poller, W. C., Schultheiss, H., Pauschinger, M., et al. (2007) · Circulation · doi:10.1161/circulationaha.106.661983 · Cited by 564
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Weber, K. T. (1997) · Circulation · doi:10.1161/01.cir.96.11.4065 · Cited by 560
Lam, C. S. P., Roger, V. L., Rodeheffer, R. J., Bursi, F., Borlaug, B. A., Ommen, S. R., Kass, D. A., & Redfield, M. M. (2007) · Circulation · doi:10.1161/circulationaha.106.659763 · Cited by 544
Cardiomyocyte stiffness in diastolic heart failure
Borbély, A., van der Velden, J., Papp, Z., Bronzwaer, J. G. F., Edes, I., Stienen, G. J. M., & Paulus, W. J. (2005) · Circulation · doi:10.1161/01.cir.0000155257.33485.6d · Cited by 536
The Pathophysiology of Heart Failure With Normal Ejection Fraction
Tan, Y. T., Wenzelburger, F., Lee, E., Heatlie, G., Leyva, F., Patel, K., Frenneaux, M. P., & Sanderson, J. E. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.03.037 · Cited by 478
Role of Left Ventricular Stiffness in Heart Failure With Normal Ejection Fraction
Westermann, D., Kašner, M., Paul Steendijk, A., Spillmann, F., Riad, A., Weitmann, K., Hoffmann, W. U., Poller, W. C., Pauschinger, M., Schultheiss, H., et al. (2008) · Circulation · doi:10.1161/circulationaha.107.716886 · Cited by 471
Self-citationMartos, R., Baugh, J. A., Ledwidge, M. T., O’Loughlin, C., Conlon, C. M., Patle, A. K., Donnelly, S. C., & McDonald, K. (2007) · Circulation · doi:10.1161/circulationaha.106.638569 · Cited by 464
Increased Collagen Type I Synthesis in Patients With Heart Failure of Hypertensive Origin
Querejeta, R., López, B., González, A., Sánchez, E., Larman, M., Ubago, J. L. M., & Dı́ez, J. (2004) · Circulation · doi:10.1161/01.cir.0000140973.60992.9a · Cited by 450
Tribouilloy, C., Ruşinaru, D., Mahjoub, H., Soulière, V., Lévy, F., Peltier, M., Slama, M., & Massy, Z. A. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehm554 · Cited by 441
Contractility and Ventricular Systolic Stiffening in Hypertensive Heart Disease
Borlaug, B. A., Lam, C. S. P., Roger, V. L., Rodeheffer, R. J., & Redfield, M. M. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.05.013 · Cited by 422
Laurent, G. J. (1987) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1987.252.1.c1 · Cited by 389
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Pauschinger, M., Knopf, D., Petschauer, S., Doerner, A., Poller, W. C., Schwimmbeck, P. L., Kühl, U., & Schultheiß, H.-P. (1999) · Circulation · doi:10.1161/01.cir.99.21.2750 · Cited by 351
Self-citationPhan, T. T., Abozguia, K., Shivu, G. N., Mahadevan, G., Ahmed, I., Williams, L. K., Dwivedi, G., Patel, K., Paul Steendijk, A., Ashrafian, H., et al. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.05.012 · Cited by 339
Matsumura, S.-I., Iwanaga, S., Mochizuki, S., Okamoto, H., Ogawa, S., & Okada, Y. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22304 · Cited by 339
Heymans, S. R. B., Hirsch, E., Anker, S. D., Aukrust, P., Balligand, J., Tervaert, J. W. C., Drexler, H., Filippatos, G. S., Felix, S. B., Gullestad, L. L., et al. (2009) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfn043 · Cited by 325
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Westermann, D., Rutschow, S., Jäger, S., Linderer, A., Anker, S. D., Riad, A., Unger, T., Schultheiß, H., Pauschinger, M., & Tschöpe, C. (2007) · Diabetes · doi:10.2337/db06-1163 · Cited by 273
Self-citationTschöpe, C., Bock, C. –., Kasner, M., Noutsias, M., Westermann, D., Schwimmbeck, P. L., Pauschinger, M., Poller, W. C., Kühl, U., Kandolf, R., et al. (2005) · Circulation · doi:10.1161/01.cir.0000155615.68924.b3 · Cited by 258
Self-citationLópez, B., González, A., Querejeta, R., Larman, M., & Dı́ez, J. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.01.077 · Cited by 249
Hall, M.-C., Young, D. A., Waters, J. G., Rowan, A. D., Chantry, A., Edwards, D. R., & Clark, I. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212334200 · Cited by 237
Westermann, D., Linthout, S. V., Dhayat, S. A., Dhayat, N. A., Schmidt, A., Noutsias, M., Song, X.-Y., Spillmann, F., Riad, A. H., Schultheiss, H. ‐., et al. (2007) · Basic Research in Cardiology · doi:10.1007/s00395-007-0673-0 · Cited by 206
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Pěnička, M., Bartúnek, J., Trakalova, H., Hrabáková, H., Maruskova, M., Karásek, J., & Kočka, V. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.11.076 · Cited by 173
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Martos, R., Baugh, J. A., Ledwidge, M. T., O’Loughlin, C., Murphy, N. F., Conlon, C. M., Patle, A. K., Donnelly, S. C., & McDonald, K. (2009) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfn036 · Cited by 134
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Heymans, S. R. B., Pauschinger, M., Palma, A. D., Kallwellis-Opara, A., Rutschow, S., Swinnen, M., Vanhoutte, D., Gao, F., Torpai, R., Baker, A. H., et al. (2006) · Circulation · doi:10.1161/circulationaha.105.591032 · Cited by 109
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Sciarretta, S., Ferrucci, A., Ciavarella, G. M., DEPAOLIS, P., Venturelli, V., Tocci, G., Biase, L. D., Rubattu, S., & Volpe, M. (2007) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2007.01.023 · Cited by 104
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Jaber, W. A., Maniu, C., Krysiak, J., Shapiro, B. P., Meyer, D. M., Linke, W. A., & Redfield, M. M. (2008) · Circulation: Heart Failure · doi:10.1161/circheartfailure.108.768465 · Cited by 33
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Tschöpe, C., & Westermann, D. (2009) · Herz · doi:10.1007/s00059-009-3197-6 · Cited by 30
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Mikko, M., Fredriksson, K., Wahlström, J., Eriksson, P. O., Grünewald, J., & Sköld, C. M. (2007) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2007.03565.x · Cited by 24
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Lisman, K. A., Stetson, S. J., Koerner, M. M., Farmer, J. A., & Torre-Amione, G. (2002) · Current Cardiology Reports · doi:10.1007/s11886-002-0051-3 · Cited by 18
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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
- Published
- 2011-01
- Volume
- 4
- Issue
- 1
- Pages
- 44-52
- ISSN
- 1941-3289 (ISSN-L)
- 1941-3297
- 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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