To explore the effect of an Ac-SDKP analog on left ventricular remodeling after myocardial infarction,we synthesized the analog Ac-SD_DK_DP by replacing Asp and Lys with their D isomers.The biological activities of Ac...To explore the effect of an Ac-SDKP analog on left ventricular remodeling after myocardial infarction,we synthesized the analog Ac-SD_DK_DP by replacing Asp and Lys with their D isomers.The biological activities of Ac-SD_DK_DP were confirmed using flow cytometry,qRT-PCR,Western blots and fluorescence microscopy.The protective effects of Ac-SD_DK_DP on infarcted hearts were assessed in mice with myocardial infarction（MI）.The half-life of Ac-SD_DK_DP was prolonged to over 2 h from a few minutes that Ac-SDKP has.Compared with Ac-SDKP,the analog exhibited stronger inhibition on the differentiation of macrophages,expression of arginase I（ARG I） and TGF-β1 in mature macrophages,proliferation and secretion of collagen type I in cardiac fibroblasts.In MI mice mode,Ac-SD_DK_DP decreased collagen deposition and TGF-β1 expression in myocardium,thus improving the FS（%） to 23.0±7.8 compared with 11.2±6.2 in untreated mice and 11.7±5.3 in Ac-SDKP treated mice（P0.05）.This work shows that the Ac-SDKP analogue is potentially useful for protective treatment for heart failure post-MI.In addition,the anti-fibrosis mechanism of Ac-SDKP was correlated with the alternative activation（M2） of macrophages by assessing ARG I and TGF-β1,two important fibrosis-related molecules secreted in M2 macrophages.展开更多
基金National Science and Technology Major Projects(Invention and Creation of New Drugs)of China 2011ZXJ09104-01BXijing project 9XJZT13M17
文摘To explore the effect of an Ac-SDKP analog on left ventricular remodeling after myocardial infarction,we synthesized the analog Ac-SD_DK_DP by replacing Asp and Lys with their D isomers.The biological activities of Ac-SD_DK_DP were confirmed using flow cytometry,qRT-PCR,Western blots and fluorescence microscopy.The protective effects of Ac-SD_DK_DP on infarcted hearts were assessed in mice with myocardial infarction（MI）.The half-life of Ac-SD_DK_DP was prolonged to over 2 h from a few minutes that Ac-SDKP has.Compared with Ac-SDKP,the analog exhibited stronger inhibition on the differentiation of macrophages,expression of arginase I（ARG I） and TGF-β1 in mature macrophages,proliferation and secretion of collagen type I in cardiac fibroblasts.In MI mice mode,Ac-SD_DK_DP decreased collagen deposition and TGF-β1 expression in myocardium,thus improving the FS（%） to 23.0±7.8 compared with 11.2±6.2 in untreated mice and 11.7±5.3 in Ac-SDKP treated mice（P0.05）.This work shows that the Ac-SDKP analogue is potentially useful for protective treatment for heart failure post-MI.In addition,the anti-fibrosis mechanism of Ac-SDKP was correlated with the alternative activation（M2） of macrophages by assessing ARG I and TGF-β1,two important fibrosis-related molecules secreted in M2 macrophages.
