Effects of bone marrow mesenchymal stem cells and Klotho gene transplantation on cardiac remodeling in chronic hypoxic rats
Author:
Affiliation:

(1. Department of Civilian Cadre’s Ward, Kunming General Hospital of Kunming Military Command, Kunming 650032, China;2. Yunnan Provincial Laboratory of Stem Cell Engineering, Kunming 650032, China)

Clc Number:

R541;R363

  • Article
  • | |
  • Metrics
  • |
  • Reference [14]
  • |
  • Related
  • | | |
  • Comments
    Abstract:

    Objective To investigate the effect of transplantation of bone marrow mesenchymal stem cells (BMSCs) and anti-aging gene (Klotho gene) on cardiac remodeling in rats under chronic hypoxic condition. Methods Rat model of cardiac remodeling was established in a hypoxic chamber of 10% oxygen for 28 d. The rats were divided into model group, BMSCs group and Klotho group, and another normal control group for isolation, culture and identification of BMSCs. Recombinant lentival vector of Klotho gene was constructed. After the establishment of the model, the BMSCs and lentival vector of Klotho were transplanted into the chronic hypoxia rats by tail vein. In 4 weeks after the infusion, the contents of procollagenⅠcarboxy-terminal propeptide (PⅠCP) and PⅢCP in the serum and myocardial tissues were detected by ELISA. The morphology of cardiomyocytes was observed by HE staining, the content of myocardial collagen was detected by MASSON staining, and the apoptotic rate of myocardial cells was detected by Tunel. SPSS statistics 17.0 was used to analyze the data. The measurement data were expressed as mean±standard deviation ([AKx-D]±s), and Student’s t test was employed for the comparison between groups. Results After 4 weeks’ transplantation of BMSCs and Klotho gene, the serum and myocardial contents of PⅠCP and PⅢCP, collagen volume fraction (CVF) and apoptotic rate of cardiomyocytes were significantly lower in the BMSCs group and Klotho group than the model group (P<0.01). Compared with the Klotho group, the BMSCs group had significantly lower apoptotic rate of myocardial cells (P<0.01). Conclusion BMSCs and Klotho gene transplantation can both effectively reverse cardiac remodeling, and BMSCs is superior to Klotho gene in resisting myocardial cell apoptosis.

    Reference
    [1] Li X, Han J, Li L, et al.Effect of farnesyltransferase inhibition on cardiac remodeling in spontaneously hypertensive rats[J].Int J Cardiol, 2013,8(4):3340-3347.DOI:10.1016/j.ijcard.2013.04.038.
    [2] Mazo M, Arana M, Pelacho B, et al.Mesenchymal stem cells and cardiovascular disease:a bench to bedside roadmap[J].Stem Cells Int, 2012,2:175979.DOI:10.1155/2012/175979.
    [3] Narita T, Suzuki K.Bone marrow derived mesenchymal stem cells for the treatment of heart failure[J].Heart Fail Rev, 2015, 20(1):53-68.DOI:10.1007/s10741-014-9435-x.
    [4] Banerjee S, Zhao Y, Sarkar PS, et al.Klotho ameliorates chemically induced endoplasmic reticulum (ER) stress signaling[J].Cell Physiol Biochem, 2013,1(4-5):659-672.DOI:10.1159/000350085.
    [5] 贾政, 魏玲, 刘茜.重组腺病毒介导Klotho基因转导对大鼠心力衰竭心肌重构的影响[J].中华心血管病杂志, 2015, 43(3):219-226.DOI:10.3760/cma.j.issn.0253-3758.2015.03.008.Jia Z, Wei L, Liu Q.Impact of transfection with recombinant adenovirus vector-mediated Klotho gene on myocardial remodeling in a rat model of heart failure[J].Chin J Cardiol, 2015,3(3):219-226.DOI:10.3760/cma.j.issn.0253-3758.2015.03.008.
    [6] 林梦娇, 田倪妮, 魏玲, 等.慢性缺氧大鼠心肌HSP47 mRNA的表达及其与PⅠCP和PⅢNP含量的相关性研究[J].中华老年多器官疾病杂志, 2017,6(4):288-292.DOI:10.11915/j.issn.1671-5403.2017.04.067.Lin MJ, Tian NN, Wei L, et al.Myocardial HSP47 mRNA expression and its correlation with serum PⅠCP and PⅢNP contents in rats under chronic hypoxic condition[J].Chin J Mult Organ Dis Elderly, 2017,6(4):288-292.DOI:10.11915/j.issn.1671-5403.2017.04.067.
    [7] 闵敏, 张雪静, 马红,等.人脂肪间充质干细胞的原代培养及体外成骨成脂诱导分化[J].江苏大学学报(医学版), 2013,3(3):185-190.Min M, Zhang XJ, Ma H, et al.Osteogenic differentiation of primary cultured human adipose-derived mesenchymal stem cells accompanying adipogenic differentiation in vitro[J].J Jiangsu Univ (Med Ed), 2013,3(3):185-190.
    [8] Krause U, Harter C, Seckinger A, et al.Intravenous delivery of autologous mesenchymal stem cells limits infarct size and improves left ventricular function in the infarcted porcine heart[J].Stem Cells Dev, 2007,6(1):31-37.
    [9] Song S, Gao P, Xiao H, et al.Klotho suppresses cardiomyocyte apoptosis in mice with stress-induced cardiac injury via downregulation of endoplasmic reticulum stress[J].PLoS One, 2013, 8(12):e82968.DOI:10.1371/journal.pone.0082968.
    [10] Li L, Zhang Y, Li Y, et al.Mesenchymal stem cell transplantation attenuates cardiac fibrosis associated with isoproterenol-induced global heart failure[J].Transplant Int, 2008,1(12):1181-1189.DOI:10.1016/0009-2509(94)00195-W.
    [11] Dixon JA, Gorman RC, Stroud RE, et al.Mesenchymal cell transplantation and myocardial remodeling following myocardial infarction[J].Circulation, 2009,0(11 Suppl):S220-S229.DOI:10.1161/CIRCULATIONAHA.108.842302.
    [12] Chang R, Li Y, Yang X, et al.Protective role of deoxyschizandrin and schisantherin A against myocardial ischemia-reperfusion injury in rats[J].PLoS One, 2013,8(4):e61590.DOI:10.1371/journal.pone.0061590.
    [13] 刘其锋, 叶建明, 李莎莎.Klotho抑制内质网应激反应减轻UUO大鼠肾间质纤维化的实验研究[J].中国中西医结合肾病杂志, 2015,6(3):203-206.Liu QF, Ye JM, Li SS.Klotho alleviates renal interstitial fibrosis via inhibition of endoplasmic reticulum stress in UUO rats[J].Chin J Integr Trad West Nephrol, 2015,6(3):203-206.
    [14] 李莎莎, 邓志勇, 何敖林,等.Klotho对CsA慢性肾毒性大鼠肾脏内质网应激相关凋亡的影响[J].生命科学研究, 2015,9(5):422-425.Li SS, Deng ZY, He AL, et al.Klotho ameliorates cyclosporine-induced chronic nephrotoxicity via inhibition of endoplasmic reticulum stress[J].Life Sci Res, 2015,9(5):422-425.[KH-*2][JY,1]
    Related
    Cited by
Get Citation
Related Videos

Share
Article Metrics
  • Abstract:
  • PDF:
  • HTML:
  • Cited by:
History
  • Received:May 15,2017
  • Revised:June 26,2017
  • Online: August 25,2017
Article QR Code