Matrix metalloproteinases and tissue remodeling in hypertrophic cardiomyopathy.
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy, myocyte disarray, and interstitial fibrosis. An increase in extracellular matrix produces interstitial fibrosis, by raised amounts of collagen type I/III. Regions of myocardial late gadolinium enhancement by cardiac magnetic resonance (CMR) represented increased myocardial collagen. Regarding the role of matrix metalloproteinases (MMPs) in myocardial remodeling and subsequent fibrosis, the aim of our study was to explore the relation between MMP system and myocardial late gadolinium enhancement by CMR (as expression of image-documented fibrosis) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (as a marker of cardiac overload) in HCM.


METHODS
We included 67 HCM patients (44 men aged 49 +/- 14 years) and were compared to 58 controls with similar age and sex. Risk factors for sudden death were recorded. A blinded CMR was performed with gadolinium. Matrix metalloproteinase 1, MMP-2, and MMP-9 plasma levels were assayed by enzyme-linked immunosorbent assay. Serum samples were used for measurement of NT-proBNP.


RESULTS
In patients, >50% of MMP-1 values were below the lowest limit of detection of the technique. Raised levels of MMP-2, MMP-9, and NT-proBNP were observed in HCM patients (all P < .01). Matrix metalloproteinase 2 was associated with dyspnea (P = .049) and correlated with MMP-9 (r = 0.28, P = .025) and NT-proBNP (r = 0.39, P = .001). Matrix metalloproteinase 9 was associated with the presence of gadolinium enhancement in CMR (P = .001) and correlated with NT-proBNP (r = 0.52, P < .001). NT-proBNP was also associated with gadolinium enhancement (P = .006). Both MMP-2 and MMP-9 correlated negatively with exercise capacity (metabolic equivalent units), (r = -0.36 and r = -0.42 respectively, both P < .01). On multivariate analysis (adjusted by sudden death risk factors and echocardiographic markers), only MMP-9 was associated with fibrosis (P = .011).


CONCLUSIONS
Matrix metalloproteinase 9 is independently associated with gadolinium enhancement on CMR in patients with hypertrophic cardiomyopathy, suggesting that the MMP system has an important role in cardiac remodeling and fibrosis in this condition.
Roldán
Vanessa
V
Centro Regional de Hemodonación, University of Murcia, Murcia, Spain.
Marín
Francisco
F
Gimeno
Juan R
JR
Ruiz-Espejo
Francisco
F
González
Josefa
J
Feliu
Eloisa
E
García-Honrubia
Antonio
A
Saura
Daniel
D
de la Morena
Gonzalo
G
Valdés
Mariano
M
Vicente
Vicente
V
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D016022:Case-Control Studies; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007089:Image Enhancement; D008279:Magnetic Resonance Imaging; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D020257:Ventricular Remodeling / Q000502:physiology*
D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D019786:Gadolinium DTPA