Difference of Gene Expression Profile of Bone Marrow Mesenchymal Stem Cells from Coronary Heart Disease Patient with or without Diabetes Mellitus_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LIU Yu , WANG Huishan , HUANG Jianhua , XUE Xiaodong , ZHANG Zhejun.

1. Department of Cardiovascular Surgery, General Hospital of Shenyang Military Command, Shenyang 110016, P.R. China;;
2. Department of Cardiovascular　Surgery, Ningxia People’s Hospital, Yinchuan 750001, P.R. China;

Corresponding author：

Keywords：

Diabetes mellitus; 　Coronary heart disease; 　Mesenchymal stem cells; 　Gene array; 　Cytokine

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Abstract：　Objective　To study the difference of gene expression profile of bone marrow mesenchymal stem cells （MSCs） cultured in vitro from coronary heart disease patient with or without diabetes mellitus by Affymetrix Gene array.　Methods　One male patient at age of 53 years with coronary heart disease and diabetes mellitus was included in this study with the diagnosis of coronary heart disease and type 2 diabetes mellitus. Another male patient at age of 51 years with coronary heart disease without diabetes mellitus was also included in this study with the diagnosis of coronary heart disease. MSCs of the two patients were isolated and purified by the methods of density gradient centrifugation with lymphocyte　separation medium for human and adherent filtration. The MSCs expression profile of cytokines and signal transduction genes were examined by Affymetrix gene array.　Results　There were 27 functional protein genes expression in the patient　with coronary heart disease and diabetes mellitus relating to cell apoptosis, cytokine, and signal transduction. Among them, the expression of 13 functional genes, including TNFRSF10B, TNFRSF21, NGF, CAV2, ITGA8, TNS1, ITGA2, AKT3, MBP, MAP2, INHBA, FST, PLA2G5, increased significantly in the patient with coronary heart disease and diabetes mellitus. However, the expression level of 14 genes, including EPR1, BIRC5, HELLS, BCL2, HGF, CASP1, SEPP1, ITGA9, MAP2K6, RUNX3, TGFBR2, RUNX2, CTNNB1, CDC42, decreased significantly.　Conclusion　The gene expression profile of bone marrow MSCs from coronary heart disease patient with diabetes mellitus is significantly different from the patient with coronary heart disease patient without diabetes mellitus.

Citation： LIU Yu,WANG Huishan,HUANG Jianhua,XUE Xiaodong,ZHANG Zhejun.. Difference of Gene Expression Profile of Bone Marrow Mesenchymal Stem Cells from Coronary Heart Disease Patient with or without Diabetes Mellitus. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2012, 19(4): 366-370. doi: Copy

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13.	Capla JM, Grogan RH, Callaghan MJ, et al. Diabetes impairs endothelial progenitor cell-mediated blood vessel formation in response to hypoxia. Plast Reconstr Surg, 2007, 119 （1）：59-70.
14.	Tepper OM, Galiano RD, Capla JM, et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation, 2002, 106 （22）：2781-2786.
15.	Klima M, Zajedova J, Doubravska L, et al. Functional analysis of the posttranslational modifications of the death receptor 6. Biochim　Biophys Acta, 2009, 1793 （10）：1579-1587.
16.	Mukherjee S, Lekli I, Das M, et al. Cardioprotection with alpha-tocopheryl phosphate： amelioration of myocardial ischemia reperfusion injury is linked with its ability to generate a survival signal through Akt activation. Biochim Biophys Acta, 2008, 1782 （9）：498-503.
17.	Martindale JJ, Wall JA, Martinez-Longoria DM, et al. Overexpression of mitogen-activated protein kinase kinase 6 in the heart improves of functional recovery from ischemia in vitro and protects against myocardial infarction in vivo. J Biol Chem, 2005, 280 （1）：669-676.
18.	Iwata A, Morgan-Stevenson V, Schwartz B, et al. Extracellular BCL2 proteins are danger-associated molecular patterns that reduce tissue damage in murine models of ischemia-reperfusion injury. PLoS One, 2010, 5 （2）：e9103.
19.	Li W, Ma N, Ong LL, et al. Bcl-2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells, 2007, 25 （8）：2118-2127.
20.	Siltanen A, Kitabayashi K, lakkisto P, et al. hHGF overexpression in myoblast sheets enhances their angiogenic potential in rat chronic heart failure. PLoS One, 2011, 6 （4）：e19161.
21.	Ellison G M, Torella D, Dellegrottaglie S, et al. Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the inrarcted pig heart. J Am Coll Cardiol, 2011, 58 （9）：977-986.
22.	Poppe A, Golsong P, Blumenthal B, et al. Hepatocyte growth factor-transfected skeletal myoblasts to limit the development of postinfarction heart failure. Artif Organs, 2012, 36 （3）：238-246.

1. 　Boilson B A, Gulati R. Stem cell therapy for the heart： a perspective. Transl Res, 2010, 155 （1）：3-5.
2. 　Kanaya AM, Grady D, Barrett-Connor E. Explaining the sex difference in coronary heart disease mortality among patients with type 2 diabetes mellitus： a meta-analysis. Arch Intern Med, 2002, 162 （15）：1737-1745.
3. 　Mazzone T, Chait A, Plutzky J. Cardiovascular disease risk in type 2 diabet mellitus： insights fromm medchanistic studies. Lancet, 2008, 371（9626）： 1800-1809.
4. 　Kestendjieva S, Kyurkchiev D, Tsvetkova G, et al. Characterization of mesenchymal stem cells isolated from the human umbilical cord. Cell Biol Int, 2008, 32 （7）： 724-732.
5. 　Kumar S, Chanda D, Ponnazhagan S. Therapeutic potential of genetically modified mesenchymal stem cells. Gene Ther, 2008, 15 （10）：711-715.
6. 　Atoui R, Asenjo JF, Duong M, et al. Marrow stromal cells as universal donor cells for myocardial regenerative therapy： their unique immune tolerance. Ann Thorac Surg, 2008, 85 （2）：571-579.
7. 　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 infracted porcine heart. Stem Cells Dev, 2007, 16 （1）：31-37.
8. 　Atoui R, Shum-Tim D, Chiu R C. Myocardial regenerative therapy： immunologic bases for the potential “universal donor cells”. Ann Thorac Surg, 2008, 86 （1）：327-334.
9. 　Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem, 2006, 98 （5）：1076-1084.
10. 　Wang M, Crisostomo P R, Herring C, et al. Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism. Am J Physiol Regul Integr Comp Physiol, 2006, 291 （4）：R880-R884.
11. 　Kupatt C, Hostkotte J, Vlastos GA, et al. Embroyonic endothelial progenitor cells expressing a broad range of proangiogenic and remodeling factors enhance vascularization and tissue recovery in acute and chronic ischemia. FASEB J, 2005, 19 （11）：1576-1578.
12. 　Gnecchi M, Zhang Z, Ni A, et al. Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res, 2008, 103 （11）：1204-1219.
13. 　Capla JM, Grogan RH, Callaghan MJ, et al. Diabetes impairs endothelial progenitor cell-mediated blood vessel formation in response to hypoxia. Plast Reconstr Surg, 2007, 119 （1）：59-70.
14. 　Tepper OM, Galiano RD, Capla JM, et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation, 2002, 106 （22）：2781-2786.
15. 　Klima M, Zajedova J, Doubravska L, et al. Functional analysis of the posttranslational modifications of the death receptor 6. Biochim　Biophys Acta, 2009, 1793 （10）：1579-1587.
16. 　Mukherjee S, Lekli I, Das M, et al. Cardioprotection with alpha-tocopheryl phosphate： amelioration of myocardial ischemia reperfusion injury is linked with its ability to generate a survival signal through Akt activation. Biochim Biophys Acta, 2008, 1782 （9）：498-503.
17. 　Martindale JJ, Wall JA, Martinez-Longoria DM, et al. Overexpression of mitogen-activated protein kinase kinase 6 in the heart improves of functional recovery from ischemia in vitro and protects against myocardial infarction in vivo. J Biol Chem, 2005, 280 （1）：669-676.
18. 　Iwata A, Morgan-Stevenson V, Schwartz B, et al. Extracellular BCL2 proteins are danger-associated molecular patterns that reduce tissue damage in murine models of ischemia-reperfusion injury. PLoS One, 2010, 5 （2）：e9103.
19. 　Li W, Ma N, Ong LL, et al. Bcl-2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells, 2007, 25 （8）：2118-2127.
20. 　Siltanen A, Kitabayashi K, lakkisto P, et al. hHGF overexpression in myoblast sheets enhances their angiogenic potential in rat chronic heart failure. PLoS One, 2011, 6 （4）：e19161.
21. 　Ellison G M, Torella D, Dellegrottaglie S, et al. Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the inrarcted pig heart. J Am Coll Cardiol, 2011, 58 （9）：977-986.
22. 　Poppe A, Golsong P, Blumenthal B, et al. Hepatocyte growth factor-transfected skeletal myoblasts to limit the development of postinfarction heart failure. Artif Organs, 2012, 36 （3）：238-246.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Difference of Gene Expression Profile of Bone Marrow Mesenchymal Stem Cells from Coronary Heart Disease Patient with or without Diabetes Mellitus

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