Alterations in the pattern of collagen deposition may contribute to the deterioration of systolic function in hypertensive patients with heart failure.
OBJECTIVE
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.
López
Begoña
B
Division of Cardiovascular Sciences, Centre for Applied Medical Research, School of Medicine, University of Navarra, Pamplona, Spain.
González
Arantxa
A
Querejeta
Ramón
R
Larman
Mariano
M
Díez
Javier
J
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002306:Cardiac Volume; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011498:Protein Precursors / Q000097:blood; D013599:Systole; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016277:Ventricular Function, Left
D010446:Peptide Fragments; D011498:Protein Precursors; D019715:Tissue Inhibitor of Metalloproteinase-1; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D003094:Collagen; D020781:Matrix Metalloproteinase 1