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. 2015 Sep 1;8(9):9836-44.
eCollection 2015.

Intermedin attenuates myocardial infarction through activation of autophagy in a rat model of ischemic heart failure via both cAMP and MAPK/ERK1/2 pathways

Peng Wei  1 , Xiang-Jun Yang  1 , Qiang Fu  2 , Bing Han  2 , Lin Ling  1 , Jie Bai  3 , Bin Zong  2 , Chun-Ying Jiang  2
Affiliations

Intermedin attenuates myocardial infarction through activation of autophagy in a rat model of ischemic heart failure via both cAMP and MAPK/ERK1/2 pathways

Peng Wei et al. Int J Clin Exp Pathol. .

Abstract

Intermedin is a proopiomelanocortin-derived peptide before opioid promoting cortical hormone, its main function embodies in mononuclear macrophages and neutrophilic granulocytes to inhibit the proinflammatory cytokines. The aim of this study is to determine intermedin attenuates myocardial infarction and its related mechanisms in a rat model of ischemic heart failure. After rat model of ischemic heart failure was set up, myocardial infarction, blood levels of activities of creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) were effectively reduced by treatment with intermedin. Tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) in a rat model of ischemic heart failure were recovered by pretreatment with intermedin. Administrate of intermedin availably promoted cAMP contents and suppressed caspase-3 protein in ischemic heart failure rat. ERK1/2 and LC3 protein expression were significantly activated and autophagy was significantly promoted by intermedin in a rat model of ischemic heart failure. These results indicate that intermedin protected rat heart, attenuates myocardial infarction from ischemic heart failure in the rat model. The underlying mechanisms may include upregulation of cAMP, ERK1/2 and LC3 protein expression and activating of autophagy.

Keywords: ERK1/2; Intermedin; autophagy; cAMP; ischemic heart failure.

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Figures

Figure 1
Figure 1
Intermedin attenuates myocardial infarction in a rat model of ischemic heart failure. Sham, Sham group; Model, ischemic heart failure model group; Intermedin, Intermedin treated group; ##P<0.01 versus the model group.
Figure 2
Figure 2
Intermedin attenuates the serum concentrations of CK, CK-MB, LDH and cTnT in a rat model of ischemic heart failure. Intermedin attenuates the serum concentrations of CK (A), CK-MB (B), LDH (C) and cTnT (D) in a rat model of ischemic heart failure. Sham, Sham group; Model, ischemic heart failure model group; Intermedin, Intermedin treated group; **P<0.01 versus the model group; ##P<0.01 versus the model group.
Figure 3
Figure 3
Intermedin attenuates the serum concentrations of TNF-α and IL-6 in a rat model of ischemic heart failure. Intermedin attenuates the serum concentrations of TNF-α (A) and IL-6 (B) in a rat model of ischemic heart failure. Sham, Sham group; Model, ischemic heart failure model group; Intermedin, Intermedin treated group; **P<0.01 versus the model group; ##P<0.01 versus the model group.
Figure 4
Figure 4
Intermedin attenuates the intracellular cAMP contents in a rat model of ischemic heart failure. Sham, Sham group; Model, ischemic heart failure model group; Intermedin, Intermedin treated group; **P<0.01 versus the model group; ##P<0.01 versus the model group.
Figure 5
Figure 5
Intermedin attenuates the caspase-3 protein in a rat model of ischemic heart failure. Intermedin attenuates the caspase-3 protein using wstern blot analysis (A), statistical analysis of caspase-3 expression (B) in a rat model of ischemic heart failure. Sham, Sham group; Model, ischemic heart failure model group; Intermedin, Intermedin treated group; **P<0.01 versus the model group; ##P<0.01 versus the model group.
Figure 6
Figure 6
Intermedin increases the ERK1/2 protein in a rat model of ischemic heart failure. Intermedin attenuates the ERK1/2 protein using wstern blot analysis (A), statistical analysis of ERK1/2 expression (B) in a rat model of ischemic heart failure. Sham, Sham group; Model, ischemic heart failure model group; Intermedin, Intermedin treated group; **P<0.01 versus the model group; ##P<0.01 versus the model group.
Figure 7
Figure 7
Intermedin activates the autophagy in a rat model of ischemic heart failure. Sham, Sham group; Model, ischemic heart failure model group; Intermedin, Intermedin treated group.
Figure 8
Figure 8
Intermedin activates the LC3 protein in a rat model of ischemic heart failure. Intermedin attenuates the LC3 protein using wstern blot analysis (A), statistical analysis of LC3 expression (B) in a rat model of ischemic heart failure. Sham, Sham group; Model, ischemic heart failure model group; Intermedin, Intermedin treated group; **P<0.01 versus the model group; ##P<0.01 versus the model group.
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