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Altered activities of atrial matrix metalloproteinases and tissue inhibitor of metalloproteinases in the pacing‐induced atrial fibrillation
Author(s) -
Chen ChienLung,
Lai ShaoChuan,
Liu ChiaWei,
Chen WenChi,
Pan ChunHsu,
Lin ChihSheng
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb20-b
Subject(s) - matrix metalloproteinase , atrial fibrillation , medicine , cardiology , pharmacology
Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) play the crucial role in extracellular matrix (ECM) metabolism and fibrosis formation in a number of cardiomyopathies, including atrial fibrillation (AF). Therefore, we examined the remodeling of MMPs (MMP‐2, MMP‐7 and MMP‐9) and TIMPs (TIMP‐1 to TIMP‐4) in the fibrillating atria of pigs. The animals with AF were induced by rapid pacing (600 bmp for 4–6 weeks) in right atrium. After the AF being induced more than for 24 hours without atrial pacing, the animals were sacrificed and the atrial tissues were isolated for assays of gel zymography and in situ zymography. The result of in situ gelatin zymography shows that strongly signal of gelatinases activity in the atria with AF as compared to the atria with sinus rhythm (SR; sham control). By the gel zymographic assay, we confirmed that the increased gelatinases activity in AF is contributed from increased MMP‐9, but not MMP‐2. Moreover, the increased expression of latent and active forms of MMP‐7 was found in the AF specimens by casein zymography analysis. Activity of the endogenous inhibitors of MMPs was also detected by reverse zymography. The total activity of TIMPs in the AF were significantly higher than that in the SR. Altered activities of MMPs and TIMPs concerning with AF was observed in this study, suggesting that regulation of MMPs and TIMPs involves in the ECM metabolism in the physiological pathogenesis of AF. This work was supported by the research grants from National Science Councils and Department of Education, Taiwan .