• Original article (Basic research) • Previous Articles     Next Articles

Effect of S1P-receptor agonist FTY720 in non-infarcted myocardium of rats

LIU Ye-hong1,2, FAN Qin1, ZHANG Feng-ru1, LU Lin1, SHEN Wei-feng1, TAO Rong1   

  1. 1.Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China； 2.Department of Cardiology, Dong Fang Hospital, Tong Ji University, Shanghai 200120, China
  • Online:2016-09-28 Published:2016-10-31
  • Supported by:

    National Natural Science Foundation of China, 81070178，813702560; Shanghai Science and Technology Key Project Grant, 12JC1406300; Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support, 20152205

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Abstract:

Objective·To analyze the effect of S1P-receptor agonist FTY720 on the expression of different receptor subtypes of S1P, explore the major receptor subtype of S1P that binds FTY720 in cardiomyocytes of rats with myocardial infarction (MI), and further investigate the protective function on non-infarcted myocardium after MI. Methods·The SD rat model of MI was constructed and SD rats were randomly allocated to sham and MI groups, both of which were further divided into three groups treated with saline, low dosage (0.04 mg/kg) of FTY720, and high dosage (0.4 mg/kg) of FTY720. Tests were performed to compare cardiac function between different groups four weeks after treatment. RT-PCR was used to measure the expressions of S1P1, S1P2, and S1P3 receptors in myocardium before and after MI and to analyze the effect of high dosage of FTY720 on the expression of S1P receptors. Histochemical staining was used to analyze the effects of FTY720 treatment on myocardial structure, interstitial fibrosis, and cell apoptosis in non-infarcted myocardium. Western blotting was conducted to detect the effect of high dosage of FTY720 on the expressions of phosphorylated AKT and ERK in non-infarcted myocardium. Results·In normal myocardium of rats without MI, S1P1 receptor was the most predominantly expressed subtype, followed by S1P3 subtype. Four weeks after MI, the expressions of S1P receptors were significantly reduced, while high dosage FTY720 treatment could remarkably elevate the expressions of S1P1 and S1P3. Similarly, FTY720 treatment could reduce pathological changes in non-infarcted myocardial tissues after MI, including cardiac remodeling, fibrosis, and cell apoptosis. Moreover, the levels of phosphorylated AKT and ERK were significantly elevated after FTY720 treatment. Conclusion·As an important agonist of S1P receptors, FTY720 may activate the AKT and ERK pathways through acting on S1P1 and S1P3 receptors in cardiomyocytes, so as to protect the non-infarcted myocardium after MI.

Key words: sphingosine 1-phosphate； FTY720, myocardial infarction