[Changes in gelatinases expression and activity in human atria during atrial fibrillation].
OBJECTIVE
To determine whether expression and activity of atrial gelatinases are altered in patients with atrial fibrillation (AF).


METHODS
The right atrial tissue samples were taken from 75 patients with rheumatic heart disease who underwent heart valve replacement surgery. 34 patients were in sinus rhythm, 11 patients had paroxysmal AF and 30 patients had persistent AF. The mRNA and protein level of MMP-2, MMP-9, TIMP-1, TIMP-2 were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western-blotting analysis respectively. The activity of MMP-2 and MMP-9 was measured by zymographic analysis.


RESULTS
(1) The mRNA level of MMP-2 increased significantly in the persistent AF group followed by the paroxysmal AF group compared with the sinus rhythm group (P < 0.01, respectively). MMP-9 mRNA expression remained compatible within groups (P > 0.05). MMP-2 and MMP-9 protein expression was prominent in the persistent AF group compared with the sinus rhythm and paroxysmal AF groups (P < 0.01), the significant difference was also observed between the paroxysmal AF and sinus groups (P < 0.05). (2) TIMP-1 and TIMP-2 expression at mRNA and protein level were all down-regulated in the persistent AF group compared with the sinus rhythm group (P < 0.05), however, the trends of reduction did not reach statistical significance in the paroxysmal AF group (P > 0.05) except that of the mRNA level of TIMP-2 (P < 0.05). (3) The activity of MMP-2 and MMP-9 significantly increased in both paroxysmal AF and persistent AF groups compared with the sinus rhythm group (P < 0.05). The significant difference in MMP-9 was also observed between the persistent AF and paroxysmal AF groups (P < 0.01). (4) MMP-2 and MMP-9 expression at mRNA and protein level were positively correlated with left atrial dimension and AF duration (P < 0.05) and were negatively correlated with the mRNA and protein level of TIMP-2 and TIMP-1 respectively (P < 0.01).


CONCLUSIONS
The upregulation of MMP-2,9 gene expression and activity, along with the selective downregulation of TIMP-1,2 may have contributed to the atrial structural remodeling during AF through influencing collagen metabolism.
Ke
Dan
D
Fujian Provincial Research Institute of Cardiovascular Diseases, Fuzhou 350001, China. kedan@vip.sina.com
Xu
Chun-Xuan
CX
Zhang
Jian-Cheng
JC
Chen
Lin
L
Lin
Ya-Zhou
YZ
Lin
Li-Fang
LF
Hu
Xi-Zhong
XZ
D000293:Adolescent; D000328:Adult; D001281:Atrial Fibrillation / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006325:Heart Atria / Q000378:metabolism*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9