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Effect of tacrolimus on myocardial infarction is associated with inflammation,ROS,MAP kinase and Akt pathways in mini-pigs
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نویسنده
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yang c.-h. ,sheu j.-j. ,tsai t.-h. ,chua s. ,chang l.-t. ,chang h.-w. ,lee f.-y. ,chen y.-l. ,chung s.-y. ,sun c.-k. ,leu s. ,yen c.-h. ,yip h.-k.
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منبع
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journal of atherosclerosis and thrombosis - 2013 - دوره : 20 - شماره : 1 - صفحه:9 -22
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چکیده
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Aim: this study tested the hypothesis that tacrolimus therapy limited left ventricular (lv) infarct and remodeling by suppressing the inflammatory response,oxidative stress and regulating the mitogen- activated protein kinase (mapk) and akt signaling pathways in an acute myocardial infarction (ami) mini-pig model by ligating the left anterior descending coronary artery (lad). methods: twelve male mini-pigs were equally randomized into ami treated by saline (3.0 ml) (amis),and ami treated by tacrolimus (0.5 mg) (amit). thirty minutes after the procedure,intra-lad injections were performed just beyond the ligation. results: inflammatory biomarkers at transcription or protein levels [matrix metalloproteinase (mmp- 9),plasminogen activator inhitor-1,tumor necrotic factor (tnf-α),nuclear factor (nf)-κb] and the cellular level (cd40+ cells) were markedly higher in amis than in amit animals (all p<0.001). fibrosis biomarkers at the protein level (α-smooth muscle actin,transforming growth factor-β) and sirius-red staining were notably higher in amis than in amit animals (all p<0.03). antioxidant biomarkers at protein or transcription levels (heme oxygenase-1,quinone oxidoreductase-1,glutathione reductase,glutathione peroxidase) were significantly higher in amis than in amit animals (all p<0.01). protein expressions of erk1,p38 mapk and akt were markedly increased in amis compared to amit animals (all p<0.001). significantly aggravated lv infarction and remodeling were noted in amis compared to amit animals,whereas lv ejection fraction was markedly decreased in amis compared to amit animals (all p<0.001). conclusions: intra-coronary administration of tacrolimus attenuated inflammation and mapk signaling,limited infarct size,and preserved lv function.
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کلیدواژه
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Experimental myocardial infarction; Inflammatory reaction; MAPK signaling pathway; Tacrolimus
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آدرس
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division of cardiology,department of internal medicine,kaohsiung chang gung memorial hospital,chang gung university college of medicine,kaohsiung, Taiwan, division of cardiovascular surgery,department of surgery,kaohsiung chang gung memorial hospital,chang gung university college of medicine,kaohsiung, Taiwan, division of cardiology,department of internal medicine,kaohsiung chang gung memorial hospital,chang gung university college of medicine,kaohsiung, Taiwan, division of cardiology,department of internal medicine,kaohsiung chang gung memorial hospital,chang gung university college of medicine,kaohsiung, Taiwan, nursing department,meiho university,pingtung, Taiwan, department of biological sciences,national sun yat-sen university,kaohsiung, Taiwan, division of cardiovascular surgery,department of surgery,kaohsiung chang gung memorial hospital,chang gung university college of medicine,kaohsiung, Taiwan, division of cardiology,department of internal medicine,kaohsiung chang gung memorial hospital,chang gung university college of medicine,kaohsiung, Taiwan, division of cardiology,department of internal medicine,kaohsiung chang gung memorial hospital,chang gung university college of medicine,kaohsiung, Taiwan, department of emergency medicine,e-da hospital,i-shou university,kaohsiung, Taiwan, center for translational research in biomedical sciences,kaohsiung chang gung memorial hospital,chang gung university college of medicine,kaohsiung, Taiwan, department of biological science and technology,national pingtung university of science and technology,pingtung, Taiwan, division of cardiology,department of internal medicine,kaohsiung chang gung memorial hospital,chang gung university college of medicine,kaohsiung, Taiwan
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Authors
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