de Souza Vieira Stella, Antonio Ednei Luiz, de Melo Brunno Lemes, Portes Leslie Andrews, Montemor Jairo, Oliveira Helenita Antônia, Martins Flavia Leticia, Zogbi Camila, Girardi Adriana Costa, Silva José Antônio, Camillo de Carvalho Paulo de Tarso, Tucci Paulo José Ferreira, Serra Andrey Jorge
Cardiology Division, Federal University of São Paulo, São Paulo, Brazil.
Cardiology Division, Federal University of São Paulo, São Paulo, Brazil; Adventist Center University of São Paulo, São Paulo, Brazil.
Heart Lung Circ. 2019 Feb;28(2):263-271. doi: 10.1016/j.hlc.2017.11.005. Epub 2017 Nov 22.
Preconditioning of cell recipients may exert a significant role in attenuating the hostility of the infarction milieu, thereby enhancing the efficacy of cell therapy. This study was conducted to examine whether exercise training potentiates the cardioprotective effects of adipose-derived stem cell (ADSC) transplantation following myocardial infarction (MI) in rats.
Four groups of female Fisher-344 rats were studied: Sham; non-trained rats with MI (sMI); non-trained rats with MI submitted to ADSCs transplantation (sADSC); trained rats with MI submitted to ADSCs (tADSC). Rats were trained 9 weeks prior to MI and ADSCs transplantation. Echocardiography was applied to assess cardiac function. Myocardial performance was evaluated in vitro. Protein expression analyses were carried out by immunoblotting. Periodic acid-Schiff staining was used to analyse capillary density and apoptosis was evaluated with terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay.
Echocardiography performed 4 weeks after the infarction revealed attenuated scar size in the both sADSC and tADSC groups compared to the sMI group. However, fractional shortening was improved only in the tADSC group. In vitro myocardial performance was similar between the tADSC and Sham groups. The expression of phosphoSer473Akt1 and VEGF were found to be higher in the hearts of the tADSC group compared to both the sADSC and sMI groups. Histologic analysis demonstrated that tADSC rats had higher capillary density in the remote and border zones of the infarcted sites compared to the sMI rats.
Preconditioning with exercise induces a pro-angiogenic milieu that may potentiate the therapeutic effects of ADSCs on cardiac remodelling following MI.
对细胞受体进行预处理可能在减轻梗死微环境的不利影响方面发挥重要作用，从而提高细胞治疗的效果。本研究旨在探讨运动训练是否能增强大鼠心肌梗死后脂肪干细胞（ADSC）移植的心脏保护作用。
研究了四组雌性Fisher-344大鼠：假手术组；心肌梗死未训练大鼠（sMI）；心肌梗死未训练且接受ADSCs移植的大鼠（sADSC）；心肌梗死训练后接受ADSCs移植的大鼠（tADSC）。在心肌梗死和ADSCs移植前9周对大鼠进行训练。应用超声心动图评估心脏功能。在体外评估心肌性能。通过免疫印迹进行蛋白质表达分析。采用过碘酸希夫染色分析毛细血管密度，并用末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）法评估细胞凋亡。
梗死后4周进行的超声心动图显示，与sMI组相比，sADSC组和tADSC组的瘢痕大小均减小。然而，仅tADSC组的缩短分数得到改善。tADSC组和假手术组的体外心肌性能相似。与sADSC组和sMI组相比，tADSC组心脏中磷酸化丝氨酸473Akt1和VEGF的表达更高。组织学分析表明，与sMI大鼠相比，tADSC大鼠梗死部位远端和边缘区的毛细血管密度更高。
运动预处理可诱导促血管生成的微环境，这可能增强ADSCs对心肌梗死后心脏重塑的治疗作用。
