CLINICAL RESEARCH: HEART FAILURE
Alterations in the Pattern of Collagen Deposition May Contribute to the Deterioration of Systolic Function in Hypertensive Patients With Heart Failure
Begoña López, PhD*,
Arantxa González, PhD*,
Ramón Querejeta, MD, PhD ,
Mariano Larman, MD and
Javier Díez, MD, PhD*, ,*
* Division of Cardiovascular Sciences, Centre for Applied Medical Research, School of Medicine, University of Navarra, Pamplona, Spain
Division of Cardiology, Donostia University Hospital, San Sebastián, Spain
Division of Hemodynamics, Guipúzcoa Polyclinics, San Sebastián, Spain
Department of Cardiology and Cardiovascular Surgery, University Clinic, University of Navarra, Pamplona, Spain.
Manuscript received November 10, 2005;
revised manuscript received December 23, 2005,
accepted January 16, 2006.
* Reprint requests and correspondence: Dr. Javier Díez, Área de Ciencias Cardiovasculares, CIMA, Pío XII 55, 31008 Pamplona, Spain. (Email: jadimar{at}unav.es).
OBJECTIVES: We sought to assess the distribution of collagen deposits and collagen degradation in hypertensive patients with either systolic heart failure (SHF) or diastolic heart failure (DHF).
BACKGROUND: Increased collagen synthesis and deposition have been described in the myocardium of heart failure (HF) hypertensive patients.
METHODS: We studied 39 HF hypertensive patients subdivided into two groups: 16 with SHF and 23 with DHF. Endomyocardial biopsies were performed to quantify mysial (i.e., perimysial plus endomysial) and perivascular and scar-related collagen volume fraction (CVF). Matrix metalloproteinase (MMP)-1 and its tissue inhibitor matrix metalloproteinase (TIMP)-1 were analyzed in cardiac samples by Western blot and immunohistochemistry, and in blood samples by enzyme-linked immunosorbent assay.
RESULTS: Mysial CVF was lower in SHF hypertensive patients than in normotensive (p < 0.05) and DHF hypertensive patients (p < 0.01). Perivascular and scar-related CVF was higher (p < 0.05) in the two groups of hypertensive patients than in normotensive subjects, and in SHF hypertensive compared with DHF hypertensive patients. The MMP-1:TIMP-1 ratio was increased (p < 0.05) in tissue and serum samples from the SHF hypertensive group compared with the other two groups of subjects. The MMP-1 expression was increased (p < 0.01) in the interstitium and cardiomyocytes of SHF hypertensive patients compared with DHF hypertensive and normotensive subjects. The serum MMP-1:TIMP-1 ratio was inversely correlated with ejection fraction (r = –0.510, p < 0.001) and directly correlated with left ventricular end-diastolic diameter (r = 0.549, p < 0.001) in all subjects.
CONCLUSIONS: These findings show that the pattern of collagen deposits and the balance of the MMP-1/TIMP-1 system are different in the myocardium of SHF and DHF hypertensive patients. It is proposed that excessive degradation of mysial collagen may be related to the compromise of systolic function in HF hypertensive patients.
|
Abbreviations and Acronyms
| | ADU = arbitrary densitometric unit | | CVF = collagen volume fraction | | DHF = diastolic heart failure | | EF = ejection fraction | | ELISA = enzyme-linked immunosorbent assay | | HF = heart failure | | LV = left ventricle/ventricular | | LVEDD = left ventricular end-diastolic diameter | | LVESWS = left ventricular end-systolic circumferential wall stress | | LVH = left ventricular hypertrophy | | LVMI = left ventricular mass index | | MMP = matrix metalloproteinase | | NT-proBNP = amino-terminal pro-brain natriuretic peptide | | SHF = systolic heart failure | | SHR = spontaneously hypertensive rat | | TIMP = tissue inhibitor matrix metalloproteinase |
|
Related Article
-
Extracellular Matrix Remodeling in Hypertensive Heart Disease
- Arsalan Shirwany and Karl T. Weber
J. Am. Coll. Cardiol. 2006 48: 97-98.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
A. Gonzalez, S. Ravassa, J. Beaumont, B. Lopez, and J. Diez
New targets to treat the structural remodeling of the myocardium.
J. Am. Coll. Cardiol.,
October 25, 2011;
58(18):
1833 - 1843.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Collier, C. J. Watson, V. Voon, D. Phelan, A. Jan, G. Mak, R. Martos, J. A. Baugh, M. T. Ledwidge, and K. M. McDonald
Can emerging biomarkers of myocardial remodelling identify asymptomatic hypertensive patients at risk for diastolic dysfunction and diastolic heart failure?
Eur J Heart Fail,
October 1, 2011;
13(10):
1087 - 1095.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Borlaug and M. M. Redfield
Diastolic and Systolic Heart Failure Are Distinct Phenotypes Within the Heart Failure Spectrum
Circulation,
May 10, 2011;
123(18):
2006 - 2014.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Lam, R. Leano, B. Haluska, and T. H. Marwick
Effects of myocardial ischaemia on left ventricular untwist and filling pressure
Heart,
May 1, 2011;
97(9):
757 - 761.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kasner, D. Westermann, B. Lopez, R. Gaub, F. Escher, U. Kuhl, H.-P. Schultheiss, and C. Tschope
Diastolic Tissue Doppler Indexes Correlate With the Degree of Collagen Expression and Cross-Linking in Heart Failure and Normal Ejection Fraction
J. Am. Coll. Cardiol.,
February 22, 2011;
57(8):
977 - 985.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Drazner
The Progression of Hypertensive Heart Disease
Circulation,
January 25, 2011;
123(3):
327 - 334.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Westermann, D. Lindner, M. Kasner, C. Zietsch, K. Savvatis, F. Escher, J. von Schlippenbach, C. Skurk, P. Steendijk, A. Riad, et al.
Cardiac Inflammation Contributes to Changes in the Extracellular Matrix in Patients With Heart Failure and Normal Ejection Fraction
Circ Heart Fail,
January 1, 2011;
4(1):
44 - 52.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Velagaleti, P. Gona, J. Sundstrom, M. G. Larson, D. Siwik, W. S. Colucci, E. J. Benjamin, and R. S. Vasan
Relations of Biomarkers of Extracellular Matrix Remodeling to Incident Cardiovascular Events and Mortality
Arterioscler Thromb Vasc Biol,
November 1, 2010;
30(11):
2283 - 2288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Jellis, J. Martin, J. Narula, and T. H. Marwick
Assessment of Nonischemic Myocardial Fibrosis
J. Am. Coll. Cardiol.,
July 6, 2010;
56(2):
89 - 97.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Gonzalez, B. Lopez, R. Querejeta, E. Zubillaga, T. Echeverria, and J. Diez
Filling Pressures and Collagen Metabolism in Hypertensive Patients With Heart Failure and Normal Ejection Fraction
Hypertension,
June 1, 2010;
55(6):
1418 - 1424.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Lopez, A. Gonzalez, and J. Diez
Circulating Biomarkers of Collagen Metabolism in Cardiac Diseases
Circulation,
April 13, 2010;
121(14):
1645 - 1654.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-C. Cheng, W.-H. L. Kao, B. D. Mitchell, J. R. O'Connell, H. Shen, P. F. McArdle, Q. Gibson, K. A. Ryan, A. R. Shuldiner, and T. I. Pollin
Genome-Wide Association Scan Identifies Variants near Matrix Metalloproteinase (MMP) Genes on Chromosome 11q21-22 Strongly Associated With Serum MMP-1 Levels
Circ Cardiovasc Genet,
August 1, 2009;
2(4):
329 - 337.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Hansson, L. Lind, J. Hulthe, and J. Sundstrom
Relations of serum MMP-9 and TIMP-1 levels to left ventricular measures and cardiovascular risk factors: a population-based study
European Journal of Cardiovascular Prevention & Rehabilitation,
June 1, 2009;
16(3):
297 - 303.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. De Silva, R. M. Wilson, C. Hutchinson, P. C. Ip, A. G. Garcia, S. Lancel, M. Ito, D. R. Pimentel, and F. Sam
Fenofibrate inhibits aldosterone-induced apoptosis in adult rat ventricular myocytes via stress-activated kinase-dependent mechanisms
Am J Physiol Heart Circ Physiol,
June 1, 2009;
296(6):
H1983 - H1993.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Gonzalez, B. Lopez, S. Ravassa, J. Beaumont, T. Arias, N. Hermida, A. Zudaire, and J. Diez
Biochemical markers of myocardial remodelling in hypertensive heart disease
Cardiovasc Res,
February 15, 2009;
81(3):
509 - 518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Hermida, B. Lopez, A. Gonzalez, J. Dotor, J. J. Lasarte, P. Sarobe, F. Borras-Cuesta, and J. Diez
A synthetic peptide from transforming growth factor-{beta}1 type III receptor prevents myocardial fibrosis in spontaneously hypertensive rats
Cardiovasc Res,
February 15, 2009;
81(3):
601 - 609.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Lopez, R. Querejeta, A. Gonzalez, J. Beaumont, M. Larman, and J. Diez
Impact of Treatment on Myocardial Lysyl Oxidase Expression and Collagen Cross-Linking in Patients With Heart Failure
Hypertension,
February 1, 2009;
53(2):
236 - 242.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Muiesan, M. Salvetti, A. Paini, C. Agabiti-Rosei, C. Monteduro, G. Galbassini, E. Belotti, C. Aggiusti, D. Rizzoni, M. Castellano, et al.
Inappropriate Left Ventricular Mass in Patients With Primary Aldosteronism
Hypertension,
September 1, 2008;
52(3):
529 - 534.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Helm, P. Caravan, B. A. French, V. Jacques, L. Shen, Y. Xu, R. J. Beyers, R. J. Roy, C. M. Kramer, and F. H. Epstein
Postinfarction Myocardial Scarring in Mice: Molecular MR Imaging with Use of a Collagen-targeting Contrast Agent
Radiology,
June 1, 2008;
247(3):
788 - 796.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Garcia-Bolao, B. Lopez, A. Macias, J. J. Gavira, P. Azcarate, and J. Diez
Impact of collagen type I turnover on the long-term response to cardiac resynchronization therapy
Eur. Heart J.,
April 1, 2008;
29(7):
898 - 906.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. G. Spinale
Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function
Physiol Rev,
October 1, 2007;
87(4):
1285 - 1342.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Lopez, A. Gonzalez, J. Beaumont, R. Querejeta, M. Larman, and J. Diez
Identification of a Potential Cardiac Antifibrotic Mechanism of Torasemide in Patients With Chronic Heart Failure
J. Am. Coll. Cardiol.,
August 28, 2007;
50(9):
859 - 867.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Muiesan, M. Salvetti, A. Paini, C. Monteduro, G. Galbassini, B. Bonzi, P. Poisa, E. Belotti, C. Agabiti Rosei, D. Rizzoni, et al.
Inappropriate Left Ventricular Mass Changes During Treatment Adversely Affects Cardiovascular Prognosis in Hypertensive Patients
Hypertension,
May 1, 2007;
49(5):
1077 - 1083.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S.P. Lam, V. L. Roger, R. J. Rodeheffer, F. Bursi, B. A. Borlaug, S. R. Ommen, D. A. Kass, and M. M. Redfield
Cardiac Structure and Ventricular-Vascular Function in Persons With Heart Failure and Preserved Ejection Fraction From Olmsted County, Minnesota
Circulation,
April 17, 2007;
115(15):
1982 - 1990.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Martos, J. Baugh, M. Ledwidge, C. O'Loughlin, C. Conlon, A. Patle, S. C. Donnelly, and K. McDonald
Diastolic Heart Failure: Evidence of Increased Myocardial Collagen Turnover Linked to Diastolic Dysfunction
Circulation,
February 20, 2007;
115(7):
888 - 895.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. N. DeMaria, O. Ben-Yehuda, G. K. Feld, G. S. Ginsburg, B. H. Greenberg, W. Y.W. Lew, J. A.C. Lima, A. S. Maisel, J. Narula, D. J. Sahn, et al.
Highlights of the Year in JACC 2006
J. Am. Coll. Cardiol.,
January 30, 2007;
49(4):
509 - 527.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Shirwany and K. T. Weber
Extracellular Matrix Remodeling in Hypertensive Heart Disease
J. Am. Coll. Cardiol.,
July 4, 2006;
48(1):
97 - 98.
[Full Text]
[PDF]
|
|
|
|
