An Ac-SDKP analogue resistant to angiotensin converting enzyme exhibits anti-fibrosis effects and improves heart function in mice after myocardial infarction

doi:10.5246/jcps.2015.12.101

Journal of Chinese Pharmaceutical Sciences ›› 2015, Vol. 24 ›› Issue (12): 789-800.DOI: 10.5246/jcps.2015.12.101

• Original articles • Previous Articles Next Articles

An Ac-SDKP analogue resistant to angiotensin converting enzyme exhibits anti-fibrosis effects and improves heart function in mice after myocardial infarction

Jianhui Chen^1,2, Xiaowen Ma³, Zhao Zhang³, Yingqi Zhang³, Yuan Yuan^2*, Meng Li^3*

1. The Ninety-first Central Hospital of the Chinese people’s liberation army, Jiaozuo 454003, China
2. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
3. Biotechnology Center, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China

Received:2015-06-16 Revised:2015-07-30 Online:2015-12-22 Published:2015-08-15
Contact: Tel.: 86-29-84773488/86-29-84775183, Fax: 86-29-83247213/86-29-84771177, E-mail: lemon781106@yahoo.com.cn, yuanfmmu@163.com
Supported by:
National Science and Technology Major Projects (Invention and Creation of New Drugs) of China 2011ZXJ09104-01B and Xijing project 9XJZT13M17.

Abstract

Abstract:

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 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.

Key words: Ac-SDKP, Analogue, Anti-fibrosis, Myocardial infarction, Heart failure

CLC Number:

R965

Supporting:

Jianhui Chen, Xiaowen Ma, Zhao Zhang, Yingqi Zhang, Yuan Yuan, Meng Li. An Ac-SDKP analogue resistant to angiotensin converting enzyme exhibits anti-fibrosis effects and improves heart function in mice after myocardial infarction[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(12): 789-800.

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An Ac-SDKP analogue resistant to angiotensin converting enzyme exhibits anti-fibrosis effects and improves heart function in mice after myocardial infarction

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