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[Effects of doxycycline on the expression of matrix metalloproteinase and tissue inhibitor of MMP in myocardium after acute myocardial infarction: an animal experiment with rats].
Zhonghua Yi Xue Za Zhi. 2004 Aug 02; 84(15):1288-93.ZY

Abstract

OBJECTIVE

To assess the effects of doxycycline, a matrix metalloproteinase (MMP) inhibitor, on the expression of MMP-8 and -13, and tissue inhibitor of MMP-1 and -2 (TIMP-1 and -2), and on collagen remodeling in the noninfarcted myocardium after acute myocardial infarction (AMI).

METHODS

212 female SD rats underwent ligation of left coronary artery so as to cause AMI. Twenty-four hours after the 127 surviving rats were randomly divided into 2 groups: AMI control group (n = 64) and AMI doxycycline treatment (30 mg.kg(-1).d(-1)) group (n = 63). Then the rats in these 2 groups were re-divided into 3 sub-groups of 18 approximately 24 rats according to the course of treatment: 1-week, 2-week, and 4-week subgroups. Thirty female SD rats underwent sham operation and then were re-divided into 3 groups of 10 rats: 1-week, 2-week, and 4-week subgroups. By the end of each course the rats were killed and their hearts were taken out. A piece of myocardium from the left ventricle was taken and stained with hematoxyline and eosin to examine the area of infarction. The mRNA expressions of MMP and TIMP in the non-infarcted myocardium were detected by RT-PCR. The protein expressions of MMP and TIMP in the non-infarcted myocardium were detected by Western blotting. The type I and type III collagen volume fraction (CVF) in the noninfarcted myocardium was examined by immunohistochemistry.

RESULTS

There was no significant difference in the MI size among the 6 subgroups of AMI control and doxycycline groups (42% approximately 48%, all P > 0.05). Compared with sham operated rats, the mRNA expressions of MMP-8 and 13 were significantly increased by 54% approximately 183% in all three subgroups of AMI controls (all P < 0.05), and the mRNA expressions of MMP-8 and 13 in the 1-week and 4-week were significantly increased by 39% approximately 160% in these 3 subgroups (all P < 0.05). The mRNA and protein expressions of TIMP-1 were enhanced only in the 1-week subgroup of AMI controls by 104% and 67% respectively (both P < 0.05). The mRNA expression of TIMP-2 was significantly increased in all 1-, 2-, and 4-week subgroups by 144% approximately 232% (all P < 0.05), however, the protein expression of TIMP-2 was increased only in the 2- and 4-week subgroups of AMI control group by 231% and 332% respectively (both P < 0.05). Compared with the sham operation group, both the type I CVF and type III CVF of the noninfarcted myocardium were significantly increased in all three subgroups of the AMI control group (type I CVF: 3.01% approximately 5.64% vs 1.53% approximately 1.67%, P < 0.01 approximately 0.001; type III CVF: 2.19% approximately 4.42% vs 1.46% approximately 1.59%, P < 0.05 approximately 0.001), with type I CVF being higher in the 4-week subgroup than in the 1 and 2-week subgroups (5.64% vs 3.01% and 3.02% respectively, all P < 0.05). In comparison with the 3 subgroups of the AMI control group, the mRNA and protein expressions of MMP-8 and 13 and TIMP-1 and 2 after AMI in the doxycycline group were significantly lower by 14% approximately 51% (all P < 0.05). In comparison with that in the AMI control group, the type I collagen deposition in the doxycycline group was significantly lower 2 and 4 weeks after AMI (1.94% vs 3.02% and 1.97% vs 5.64% respectively, P < 0.01 approximately 0.001), however, there was no significant difference in type III CVF among the different subgroups (all P > 0.05).

CONCLUSION

Doxycycline suppresses the enhanced mRNA and protein expressions of MMP-8 and 13 and TIMP-1 and 2, and type I collagen deposition in the noninfarcted myocardium after AMI, but it has no effect on type III collagen deposition.

Authors+Show Affiliations

Department of Coronary Heart Disease, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

15387968

Citation

Zhang, Pei, et al. "[Effects of Doxycycline On the Expression of Matrix Metalloproteinase and Tissue Inhibitor of MMP in Myocardium After Acute Myocardial Infarction: an Animal Experiment With Rats]." Zhonghua Yi Xue Za Zhi, vol. 84, no. 15, 2004, pp. 1288-93.
Zhang P, Yang YJ, Chen X, et al. [Effects of doxycycline on the expression of matrix metalloproteinase and tissue inhibitor of MMP in myocardium after acute myocardial infarction: an animal experiment with rats]. Zhonghua Yi Xue Za Zhi. 2004;84(15):1288-93.
Zhang, P., Yang, Y. J., Chen, X., Ruan, Y. M., Zhou, Y. W., Tian, Y., & Chen, Z. J. (2004). [Effects of doxycycline on the expression of matrix metalloproteinase and tissue inhibitor of MMP in myocardium after acute myocardial infarction: an animal experiment with rats]. Zhonghua Yi Xue Za Zhi, 84(15), 1288-93.
Zhang P, et al. [Effects of Doxycycline On the Expression of Matrix Metalloproteinase and Tissue Inhibitor of MMP in Myocardium After Acute Myocardial Infarction: an Animal Experiment With Rats]. Zhonghua Yi Xue Za Zhi. 2004 Aug 2;84(15):1288-93. PubMed PMID: 15387968.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Effects of doxycycline on the expression of matrix metalloproteinase and tissue inhibitor of MMP in myocardium after acute myocardial infarction: an animal experiment with rats]. AU - Zhang,Pei, AU - Yang,Yue-jin, AU - Chen,Xi, AU - Ruan,Ying-mao, AU - Zhou,Yan-wen, AU - Tian,Yi, AU - Chen,Zai-jia, PY - 2004/9/25/pubmed PY - 2005/8/27/medline PY - 2004/9/25/entrez SP - 1288 EP - 93 JF - Zhonghua yi xue za zhi JO - Zhonghua Yi Xue Za Zhi VL - 84 IS - 15 N2 - OBJECTIVE: To assess the effects of doxycycline, a matrix metalloproteinase (MMP) inhibitor, on the expression of MMP-8 and -13, and tissue inhibitor of MMP-1 and -2 (TIMP-1 and -2), and on collagen remodeling in the noninfarcted myocardium after acute myocardial infarction (AMI). METHODS: 212 female SD rats underwent ligation of left coronary artery so as to cause AMI. Twenty-four hours after the 127 surviving rats were randomly divided into 2 groups: AMI control group (n = 64) and AMI doxycycline treatment (30 mg.kg(-1).d(-1)) group (n = 63). Then the rats in these 2 groups were re-divided into 3 sub-groups of 18 approximately 24 rats according to the course of treatment: 1-week, 2-week, and 4-week subgroups. Thirty female SD rats underwent sham operation and then were re-divided into 3 groups of 10 rats: 1-week, 2-week, and 4-week subgroups. By the end of each course the rats were killed and their hearts were taken out. A piece of myocardium from the left ventricle was taken and stained with hematoxyline and eosin to examine the area of infarction. The mRNA expressions of MMP and TIMP in the non-infarcted myocardium were detected by RT-PCR. The protein expressions of MMP and TIMP in the non-infarcted myocardium were detected by Western blotting. The type I and type III collagen volume fraction (CVF) in the noninfarcted myocardium was examined by immunohistochemistry. RESULTS: There was no significant difference in the MI size among the 6 subgroups of AMI control and doxycycline groups (42% approximately 48%, all P > 0.05). Compared with sham operated rats, the mRNA expressions of MMP-8 and 13 were significantly increased by 54% approximately 183% in all three subgroups of AMI controls (all P < 0.05), and the mRNA expressions of MMP-8 and 13 in the 1-week and 4-week were significantly increased by 39% approximately 160% in these 3 subgroups (all P < 0.05). The mRNA and protein expressions of TIMP-1 were enhanced only in the 1-week subgroup of AMI controls by 104% and 67% respectively (both P < 0.05). The mRNA expression of TIMP-2 was significantly increased in all 1-, 2-, and 4-week subgroups by 144% approximately 232% (all P < 0.05), however, the protein expression of TIMP-2 was increased only in the 2- and 4-week subgroups of AMI control group by 231% and 332% respectively (both P < 0.05). Compared with the sham operation group, both the type I CVF and type III CVF of the noninfarcted myocardium were significantly increased in all three subgroups of the AMI control group (type I CVF: 3.01% approximately 5.64% vs 1.53% approximately 1.67%, P < 0.01 approximately 0.001; type III CVF: 2.19% approximately 4.42% vs 1.46% approximately 1.59%, P < 0.05 approximately 0.001), with type I CVF being higher in the 4-week subgroup than in the 1 and 2-week subgroups (5.64% vs 3.01% and 3.02% respectively, all P < 0.05). In comparison with the 3 subgroups of the AMI control group, the mRNA and protein expressions of MMP-8 and 13 and TIMP-1 and 2 after AMI in the doxycycline group were significantly lower by 14% approximately 51% (all P < 0.05). In comparison with that in the AMI control group, the type I collagen deposition in the doxycycline group was significantly lower 2 and 4 weeks after AMI (1.94% vs 3.02% and 1.97% vs 5.64% respectively, P < 0.01 approximately 0.001), however, there was no significant difference in type III CVF among the different subgroups (all P > 0.05). CONCLUSION: Doxycycline suppresses the enhanced mRNA and protein expressions of MMP-8 and 13 and TIMP-1 and 2, and type I collagen deposition in the noninfarcted myocardium after AMI, but it has no effect on type III collagen deposition. SN - 0376-2491 UR - https://www.unboundmedicine.com/medline/citation/15387968/[Effects_of_doxycycline_on_the_expression_of_matrix_metalloproteinase_and_tissue_inhibitor_of_MMP_in_myocardium_after_acute_myocardial_infarction:_an_animal_experiment_with_rats]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&amp;issn=0376-2491&amp;year=2004&amp;vol=84&amp;issue=15&amp;fpage=1288 DB - PRIME DP - Unbound Medicine ER -