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

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.