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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

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