Down-regulation of matrix metalloproteinase-9 (MMP-9) expression in the myocardium of congestive heart failure patients.
Matrix metalloproteinases (MMPs) are proteolytic enzymes responsible for extracellular matrix protein degradation. They have an important role in tissue remodeling processes. Their activity is regulated at the transcriptional, translational, and posttranslational level and by tissue inhibitors (TIMPs). Our aim was to analyze whether expression changes in MMPs that degrade collagens and their inhibitors in the myocardium have an impact on ventricular remodeling and the fibrogenesis in congestive heart failure.


METHODS
We analyzed left ventricle biopsies from 18 patients with idiopathic dilated cardiomyopathy (iCDM) and severe congestive heart failure (HF) and 13 biopsies from organ donors. mRNA expression was quantified by real-time PCR, and fibrosis levels measured with picrosirius red staining.


RESULTS
The patients mean age was 53 +/- 3 years. Expression levels of MMP-1, MMP-2, MMP-3, and TIMP1 did not show differences in pathological hearts compared to control hearts. Expression levels of MMP-1 and MMP-3 were low. MMP-9 expression levels were down-regulated in the cardiomyopathic hearts (49.77 +/- 7.6 ng equivalents of cDNA [ng-eq]) compared to controls (91.24 +/- 10.8 ng-eq, P < .005). MMP-2 expression levels correlated with the fibrosis levels (P < .05, R2 = 0.33, n = 18).


CONCLUSIONS
MMP-9 mRNA expression down-regulation suggested that the protein levels were regulated at the posttranscriptional level. The correlation between MMP-2 expression levels and the collagen fraction in the pathological hearts indicated a putative role of MMP-2 in the fibrosis that takes place in congestive heart failure.
Batlle
M
M
Institut Clinic del Tòrax and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Barcelona, Spain. mbatlle@clinic.ub.es
Pérez-Villa
F
F
García-Pras
E
E
Lázaro
A
A
Orús
J
J
Roqué
M
M
Roig
E
E
D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D006333:Heart Failure / Q000201:enzymology* / Q000235:genetics; D016027:Heart Transplantation / Q000502:physiology*; D006352:Heart Ventricles / Q000201:enzymology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D020782:Matrix Metalloproteinases / Q000235:genetics; D014176:Protein Biosynthesis; D014158:Transcription, Genetic
D018076:DNA, Complementary; D003094:Collagen; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9