Abstract:
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.
journal_name
J Atheroscler Thrombjournal_title
Journal of atherosclerosis and thrombosisauthors
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 HKdoi
10.5551/jat.14316subject
Has Abstractpub_date
2013-01-01 00:00:00pages
9-22issue
1eissn
1340-3478issn
1880-3873pii
DN/JST.JSTAGE/jat/14316journal_volume
20pub_type
杂志文章abstract:AIM:Angiotensin (Ang) II-induced abdominal aortic aneurysm (AAA) in apoE-deficient mice has been used as a model of human AAA, but it has been unclear why the progression of AAA continues after stopping the Ang II infusion. The involvement of vascular Ang II-forming enzymes in the progression of AAA was studied. METHO...
journal_title:Journal of atherosclerosis and thrombosis
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journal_title:Journal of atherosclerosis and thrombosis
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journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Journal of atherosclerosis and thrombosis
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journal_title:Journal of atherosclerosis and thrombosis
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journal_title:Journal of atherosclerosis and thrombosis
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