Abstract:
:The novel biological effect of statins in alleviating myocardium fibrosis following infarction has been increasingly recognized, yet the underlying mechanisms are not fully understood. The purpose of this study was to characterize the effect of simvastatin on myocardial fibrosis and collagen I deposition in the non-infarcted region after myocardial infarction (MI) and to identify the role of NF-κB and osteopontin in simvastatin-mediated inhibition of post-MI collagen over-expression. A rat model of MI was generated by ligating the left anterior descending coronary artery. The rats surviving the MI operation were randomly divided into the following 3 groups: myocardial infarction (MI, vehicle), simvastatin (Sim, 30 mg·kg-1·day-1), and pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB, 100 mg·kg-1·day-1). Four weeks after MI, cardiac function, mRNAs, and protein expression in non-infarcted myocardium were analyzed. Myocardial fibrosis and collagen I over-expression were observed following MI, accompanied by an increase of NF-κB and osteopontin. Simvastatin improved post-MI left ventricular dysfunction and ameliorated post-MI associated changes to several cardiac parameters, including the left ventricular end diastolic pressure (LVEDP), the maximal rate of pressure development (+dP/dtmax), and the maximal rate of pressure decline (-dP/dtmax). Concurrently, simvastatin significantly suppressed the over-expression of NF-κB, osteopontin, and collagen I in the non-infarcted region following MI. Inhibition of NF-κB by PDTC also reduced osteopontin over-expression and excessive collagen I production and improved the above functional myocardial parameters. These results show that post-MI myocardial fibrosis and collagen I over-expression in the non-infarcted region is associated with activation of NF-κB and osteopontin up-regulation. The anti-fibrotic effect of simvastatin following MI is associated with the attenuation of the expression of osteopontin and NF-κB. The inhibition of NF-κB activation could be the process upstream of osteopontin suppression in the simvastatin-mediated effect.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Zhang J,Xu Y,Pan L,Chen T,Chen Z,Zhao Rdoi
10.1139/y10-075subject
Has Abstractpub_date
2010-11-01 00:00:00pages
1026-34issue
11eissn
0008-4212issn
1205-7541pii
y10-075journal_volume
88pub_type
杂志文章abstract::There are conflicting reports concerning the existence of severe hypermethioninemia in rats made diabetic with the pancreotoxin, streptozotocin. To determine whether this discrepancy is due to experimental differences in the severity of diabetes or the diet fed to the animals, streptozotocin-diabetic and control rats ...
journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y91-008
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y91-026
更新日期:1991-02-01 00:00:00
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y87-388
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pub_type: 杂志文章,评审
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journal_title:Canadian journal of physiology and pharmacology
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
doi:10.1139/y92-025
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journal_title:Canadian journal of physiology and pharmacology
pub_type: 杂志文章
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