[Effects of matrix metalloproteinase-9 and tissue inhibitor-1 of metalloproteinase expression on atrial structural remodeling during chronic atrial fibrillation].
OBJECTIVE
To investigate the matrix metalloproteinase-9 (MMP-9) and tissue inhibitor-1 of metalloproteinase (TIMP-1) mRNA and protein expression in chronic fibrillating human atria and to evaluate the influence of MMP-9 and TIMP-1 expression on the progress of atrial structural remodeling.


METHODS
Twenty-four patients with chronic atrial fibrillation (AF) and 12 patients with sinus rhythm as control group underwent transthoracic echocardiography and left atrial appendage (LAA) tissue samples were obtained from these patients during mitral/aortic valve replacement operation. MMP-9 and TIMP-1 protein expressions were detected by immunohistochemistry and their mRNA expressions were determined by reverse transcription polymerase chain reaction (RT-PCR).


RESULTS
The left atrial and right atrial diameters increased significantly in the fibrillation group in comparison with the control group (57 +/- 6 vs 45 +/- 7, 62 +/- 10 vs 51 +/- 17, P < 0.05 approximately 0.001) The expressions of MMP-9 mRNA and protein in the LAA tissue of the AF group is upregulated (0.70 +/- 0.12 vs 0.53 +/- 0.22, and 2.25 +/- 0.73 vs 1.12 +/- 0.58, P < 0.05 approximately 0.001) and the expressions of TIMP-1 mRNA and protein were downregulated significantly (0.20 +/- 0.07 vs 0.31 +/- 0.15, and 1.12 +/- 0.48 vs 1.75 +/- 0.46, P < 0.05 approximately 0.01). The MMP-9 mRNA level was positively correlated with AF duration and the left atrial diameter (P < 0.05 approximately 0.001).


CONCLUSIONS
There is a selective downregulation of TIMP-1 expression along with the upregulation of MMP-9 in AF, which indicates that the disturbance expression of MMP/TIMP system may promote the process of atrial structural remodeling. Enhanced MMP-9 activity may be a molecular mechanism contributing to the dilation of fibrillating human atria.
Zhu
Hui
H
Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, China.
Zhang
Wei
W
Guo
Chen-Hong
CH
Zhang
Gong
G
Zhang
Wei-Dong
WD
Zhong
Ming
M
Yang
Gui-Rong
GR
Ge
Zhi-Ming
ZM
Zhang
Yun
Y
D000328:Adult; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016275:Atrial Function; D004452:Echocardiography; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9