Effect of tacrolimus on myocardial infarction is associated with inflammation, ROS, MAP kinase and Akt pathways in mini-pigs

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题名:	Effect of tacrolimus on myocardial infarction is associated with inflammation, ROS, MAP kinase and Akt pathways in mini-pigs
作者:	Yang CH;Sheu JJ;Tsai TH;Chua S;Chang LT;Chang HW;Lee FY;Chen YL;Chung SY;Sun CK;Leu S;Yen CH;Yip HK
日期:	2013
上传时间:	2013-10-03T07:33:45Z (UTC)
摘要:	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) (AMI(S)), and AMI treated by tacrolimus (0.5 mg) (AMI(T)). Thirty minutes after the procedure, intra-LAD injections were performed just beyond the ligation. RESULTS: Inflammatory biomarkers at transcription or protein levels [matrix metalloproteinase (MMP9), plasminogen activator inhitor-1, tumor necrotic factor (TNF-α), nuclear factor (NF)-κB] and the cellular level (CD40+ cells) were markedly higher in AMI(S) than in AMI(T) 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 AMI(S) than in AMI(T) 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 AMI(S) than in AMI(T) animals (all p<0.01). Protein expressions of ERK1, p38 MAPK and Akt were markedly increased in AMI(S) compared to AMI(T) animals (all p<0.001). Significantly aggravated LV infarction and remodeling were noted in AMI(S) compared to AMI(T) animals, whereas LV ejection fraction was markedly decreased in AMI(S) compared to AMI(T) animals (all p<0.001). CONCLUSIONS: Intra-coronary administration of tacrolimus attenuated inflammation and MAPK signaling, limited infarct size, and preserved LV function.
關聯:	J Atheroscler Thromb. 2013;20(1):9-22
显示于类别:	[護理系] 期刊論文

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