Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Original Article
Effect of Tacrolimus on Myocardial Infarction Is Associated with Inflammation, ROS, MAP Kinase and Akt Pathways in Mini-Pigs
Cheng-Hsu YangJiunn-Jye SheuTzu-Hsien TsaiSarah ChuaLi-Teh ChangHsueh-Wen ChangFan-Yen LeeYung-Lung ChenSheng-Ying ChungCheuk-Kwan SunSteve LeuChia-Hung YenHon-Kan Yip
ジャーナル フリー

2013 年 20 巻 1 号 p. 9-22


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 (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).
Conclusions: Intra-coronary administration of tacrolimus attenuated inflammation and MAPK signaling, limited infarct size, and preserved LV function.


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