Abstract: | To explore the effect of an Ac-SDKP analog on left ventricular remodeling after myocardial infarction, we synthesized the analog Ac-SDDKDP by replacing Asp and Lys with their D isomers. The biological activities of Ac-SDDKDP were confirmed using flow cytometry, qRT-PCR, Western blots and fluorescence microscopy. The protective effects of Ac-SDDKDP on infarcted hearts were assessed in mice with myocardial infarction (MI). The half-life of Ac-SDDKDP 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-SDDKDP decreased collagen deposition and TGF-β1 expression in myocardium, thus improvingthe 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 (P<0.05). 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. |