Effect of Tacrolimus on Myocardial Infarction Is Associated with Inflammation, ROS, MAP Kinase and Akt Pathways in Mini-Pigs
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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).<BR>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.<BR>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 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).<BR>Conclusions: Intra-coronary administration of tacrolimus attenuated inflammation and MAPK signaling, limited infarct size, and preserved LV function.
- 一般社団法人 日本動脈硬化学会の論文
一般社団法人 日本動脈硬化学会 | 論文
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