Alterations in the Pattern of Collagen Deposition May Contribute to the Deterioration of Systolic Function in Hypertensive Patients With Heart Failure
Received 10 November 2005; received in revised form 23 December 2005; accepted 16 January 2006. published online 12 June 2006.
Alterations in the Pattern of Collagen Deposition May Contribute to the Deterioration of Systolic Function in Hypertensive Patients With Heart Failure
Begoña López, Arantxa González, Ramón Querejeta, Mariano Larman, Javier Díez
Endomyocardial biopsies were performed to assess collagen deposits and matrix metalloproteinase (MMP)-1 and its tissue inhibitor matrix metalloproteinase (TIMP)-1 expression in 39 heart failure (HF) hypertensive patients subdivided into two groups: 16 with ejection fraction (EF) <0.40 (systolic heart failure [SHF]) and 23 with EF ≥0.40 (diastolic heart failure [DHF]). We found that an excess of MMP-1 relative to TIMP-1 is associated with diminished perimysial and endomysial collagen deposition in SHF hypertensive patients, but not in DHF hypertensive subjects. Thus, differential regulation of collagen degradation may be one of the factors determining the type of HF in hypertensive patients.
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.
⁎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.
Reprint requests and correspondence: Dr. Javier Díez, Área de Ciencias Cardiovasculares, CIMA, Pío XII 55, 31008 Pamplona, Spain.
This work was supported by a grant from the UTE Project FIMA and by grant RECAVA C03/01 from the Fondo de Investigaciones Sanitarias, Ministry of Health, Spain. Drs. López and González contributed equally to this work.
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