Increased matrix metalloproteinase-8 and -9 activity in patients with infarct rupture after myocardial infarction.
BACKGROUND
Infarct rupture is a usually fatal complication of myocardial infarction (MI), for which no molecular mechanism has been described in humans. Experimental evidence in mouse models suggests that the degradation of the extracellular matrix by matrix metalloproteinases (MMPs) plays an important role in infarct rupture. The present study was designed to study the role of MMP-2, MMP-8, and MMP-9 in human infarct rupture.


METHODS
Heart samples were obtained from patients who died from infarct rupture and control MI patients. The MMP activity was determined by zymography and quantitative immunocapture activity assay. TIMP-1 levels were measured and immunohistochemistry for MMP-2 and MMP-9 was performed.


RESULTS
The amounts of both total and active MMP-8 and MMP-9 were significantly higher in ruptured infarct tissue than in control MI tissue, but no differences in MMP-2 activity were observed. Furthermore, the number of inflammatory cells was significantly higher in the ruptured infarcts than in control infarcts.


CONCLUSIONS
These data suggest that increased MMP-8 and MMP-9 activity in the infarct area, caused by a more prominent infiltration of inflammatory cells, contribute to infarct rupture in humans.
van den Borne
Susanne W M
SW
Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Cleutjens
Jack P M
JP
Hanemaaijer
Roeland
R
Creemers
Esther E
EE
Smits
Jos F M
JF
Daemen
Mat J A P
MJ
Blankesteijn
W Matthijs
WM
D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D005260:Female; D006342:Heart Rupture, Post-Infarction / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D009205:Myocarditis / Q000473:pathology
C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9