Effect of carvedilol on cardiac metalloproteinases and tissue inhibitors of metalloproteinases after myocardial infarction in rats
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    Abstract:

    Objective:To investigate the effect of carvedilol on expression of cardiac matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) after myocardial infarction in rats. Methods: An animal model of acute myocardial infarction (AMI) was established by descending left coronary artery ligation in 24 rats and they were divided into carvedilol (10 mg·kg-1·d-1) group (n=12) and normal saline group (n=12). Sham-operated group (n=9) received the same procedure but with no ligation. All animals were treated for 6 weeks via a gastric lavage. Heart function and hemodynamic parameters were determined after 6 weeks.The protein expression of cardiac MMP-2, MMP-9 and TIMP-2 was detected by immunohistochemical analysis in AMI groups, and the MMPs activities were assessed by zymography. Gene expression of myocardial MMPs/TIMPs (MMP-2,-9 and TIMP-1, -2) and cytokines (TNF-α, IL-1β) were measured by real-time quantitative PCR. Results: Compared with Sham-operated group,carvedilol group had significantly higher left ventricular end-diastolic pressure (LVEDP) and lower LV upstroke velocity (+dp/dtmax) and LV descent velocity (-dp/dtmax)(P<0.01). Activities of MMP-2 and MMP-9, protein expression of MMP-2, MMP-9 and TIMP-2, and mRNA expression of MMP-2, MMP-9, TIMP-1, TIMP-2, IL-1β, and TNF-α were all higher in carvedilol group compared with sham-operated group (P<0.05). Compared with normal saline group, carvedilol group had lower LVEDP(P<0.01), higher +dp/dtmax, -dp/dtmax(P<0.05),lower activities of MMP-2, MMP-9(P<0.01), lower protein expression of MMP-2, MMP-9 and TIMP-2, and lower mRNA expression of MMP-2, MMP-9, TIMP-2, IL-1β, TIMP-1, and TNF-α (MMP-9 P<0.01,others P<0.05). Conclusion: Carvedilol can obviously decrease cardiac expression of MMP-2 and MMP-9 and slightly decrease expression of TIMPs; it can also decrease secretion of MMPs through decreasing IL-1β and TNF-α expression,thus prevents myocardial extracellular matrix remodeling,reverses ventricular remodeling,and subsequently improves cardiac function.

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History
  • Received:July 03,2007
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  • Online: April 16,2008
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