Matrix metalloproteinase-9 contributes to human atrial remodeling during atrial fibrillation.
OBJECTIVE
The purpose of this study was to determine the relationship between matrix metalloproteinases (MMPs)-1, -2, and -9, and tissue inhibitors of metalloproteinases (TIMP)-1 and the atrial structural remodeling during atrial fibrillation (AF).


BACKGROUND
Matrix metalloproteinases, a family of proteolytic enzymes and TIMPs, regulate the extracellular matrix turnover in cardiac tissue.


METHODS
Tissue samples were obtained from 25 patients without a history of AF (regular sinus rhythm [RSR]) and 13 patients with AF (paroxysmal AF: 6, chronic AF 7) undergoing cardiac operations. We performed a western blotting analysis of the MMP-1, -2, and -9, and quantitatively analyzed the expression of the MMP-9 and TIMP-1 by real time polymerase chain reaction and ELISA. The localization of the MMP-9 was investigated by in situ zymography and immunohistochemistry.


RESULTS
The active form of the MMP-9 was significantly increased in the AF group in comparison to that in the RSR group (p < 0.05), but there were no differences between the groups in the protein level of the latent form of the MMP-9 and active and latent forms of the MMP-1 and MMP-2. We also demonstrated that the expression of the MMP-9 was significantly more increased in the atria of the AF group than in that of the RSR group for both the messenger ribonucleic acid (mRNA) (AF: RSR; 1: 1.5) and protein levels (AF: RSR; 3.9 +/- 1.3 : 1.5 +/- 0.4 ng/mg atrium). The expression level of the MMP-9 was also higher in the PAF group than in the RSR group, however, the diameter of the left atrium was similar in both groups. The gelatinase activity and left atrium diameter were positively correlated (p < 0.05, R = 0.766). The relative expression of the mRNA for the monocyte chemoattractant protein-1 was higher in the AF group than in the RSR group. Immunohistochemical analysis revealed that the MMP-9 was distributed within the perivascular area and under the epicardium of the atria.


CONCLUSIONS
We clearly showed that the expression of the MMP-9 increased in fibrillating atrial tissue, which may have contributed to the atrial structural remodeling and atrial dilatation during AF.
Nakano
Yukiko
Y
Department of Medicine and Molecular Science, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. ynakano@xj8.so-net.ne.jp
Niida
Shumpei
S
Dote
Keigo
K
Takenaka
Sou
S
Hirao
Hidekazu
H
Miura
Fumiharu
F
Ishida
Mari
M
Shingu
Tetsuji
T
Sueda
Taijiro
T
Yoshizumi
Masao
M
Chayama
Kazuaki
K
D000368:Aged; D001281:Atrial Fibrillation / Q000473:pathology / Q000503:physiopathology*; D016275:Atrial Function; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1