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http://dx.doi.org/10.4070/kcj.2016.46.1.79

Changes in Caspase-3, B Cell Leukemia/Lymphoma-2, Interleukin-6, Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor Gene Expression after Human Umbilical Cord Blood Derived Mesenchymal Stem Cells Transfusion in Pulmonary Hypertension Rat Model  

Kim, Kwan Chang (Department of Thoracic and Cardiovascular Surgery, Ewha Womans University School of Medicine)
Lee, Jae Chul (Department of Pediatrics, Ewha Womans University School of Medicine)
Lee, Hyeryon (Department of Pediatrics, Ewha Womans University School of Medicine)
Cho, Min-Sun (Department of Pathology, Ewha Womans University School of Medicine)
Choi, Soo Jin (Biomedical Research Institute, MEDIPOST, Co.)
Hong, Young Mi (Department of Pediatrics, Ewha Womans University School of Medicine)
Publication Information
Korean Circulation Journal / v.46, no.1, 2016 , pp. 79-92 More about this Journal
Abstract
Background and Objectives: Failure of vascular smooth muscle apoptosis and inflammatory response in pulmonary arterial hypertension (PAH) is a current research focus. The goals of this study were to determine changes in select gene expressions in monocrotaline (MCT)-induced PAH rat models after human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) transfusion. Materials and Methods: The rats were separated into 3 groups i.e., control group (C group), M group (MCT 60 mg/kg), and U group (hUCB-MSCs transfusion) a week after MCT injection. Results: TUNEL assay showed that the U group had significantly lowered positive apoptotic cells in the lung tissues, as compared with the M group. mRNA of caspase-3, B cell leukemia/lymphoma (Bcl)-2, interleukin (IL)-6, tumor necrosis factor (TNF)-${\alpha}$ and vascular endothelial growth factor (VEGF) in the lung tissues were greatly reduced at week 4 in the U group. Immunohistochemical staining of the lung tissues also demonstrated a similar pattern, with the exception of IL-6. The protein expression of caspase-3, Bcl-2 VEGF, IL-6, TNF-${\alpha}$ and brain natriuretic peptide in the heart tissues were significantly lower in the U group, as compared with the M group at week 2. Furthermore, the protein expression of VEGF, IL-6 and BNP in the heart tissues were significantly lower in the U group at week 4. Collagen content in the heart tissues was significantly lower in the U group, as compared with M group at weeks 2 and 4, respectively. Conclusion: hUCB-MSCs could prevent inflammation, apoptosis and remodeling in MCT-induced PAH rat models.
Keywords
Hypertension, pulmonary; Stem cell; Vascular remodeling; Inflammation; Apoptosis;
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1 Grosjean J, Kiriakidis S, Reilly K, Feldmann M, Paleolog E. Vascular endothelial growth factor signalling in endothelial cell survival: a role for NFkappaB. Biochem Biophys Res Commun 2006;340:984-94.   DOI
2 Bogaard HJ, Abe K, Vonk Noordegraaf A, Voelkel NF. The right ventricle under pressure: cellular and molecular mechanisms of rightheart failure in pulmonary hypertension. Chest 2009;135:794-804.   DOI
3 Krown KA, Page MT, Nguyen C, et al. Tumor necrosis factor-induced apoptosis in cardiac myocytes: involvement of the sphingolipid signaling cascade in cardiac cell death. J Clin Invest 1996;98:2854-65.   DOI
4 Kret M, Arora R. Pathophysiological basis of right ventricular remodeling. J Cardiovasc Pharmacol Ther 2007;12:5-14.   DOI
5 Kucuker SA, Stetson SJ, Becker KA, et al. Evidence of improved right ventricular structure after LVAD support in patients with end-stage cardiomyopathy. J Heart Lung Transplant 2004;23:28-35.   DOI
6 Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation 2004;109:159-65.   DOI
7 Ryan JJ, Huston J, Kutty S, et al. Right ventricular adaptation and failure in pulmonary arterial hypertension. Can J Cardiol 2015;31:391-406.   DOI
8 Rojas M, Xu J, Woods CR. et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Stem Cell Mol Biol 2005; 33:145-52.   DOI
9 Lee JC, Kim KC, Yang YS, et al. Microarray analysis after umbilical cord blood derived mesenchymal stem cells injection in monocrotalineinduced pulmonary artery hypertension rats. Anat Cell Biol 2014;47:217-26.   DOI
10 Chang YS, Oh W, Choi SJ. Human umbilical cord blood-derived mesenchymal stem cells attenuate hyperoxia-induced lung injury in neonatal rats. Cell Transplant 2009;18:869-86.   DOI
11 Ortiz LA,.Gambelli F, McBride C, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci USA 2003; 100:8407-11.   DOI
12 Sakao S, Taraseviciene-Stewart L, Lee JD, Wood K, Cool CD, Voelkel NF. Initial apoptosis is followed by increased proliferation of apoptosis-resistant endothelial cells. FASEB J 2005;19:1178-80.   DOI
13 Jurasz P, Courtman D, Babaie S, Stewart DJ. Role of apoptosis in pulmonary hypertension: from experimental models to clinical trials. Pharmacol Ther 2010;126:1-8.   DOI
14 Jeffery TK, Morrell NW. Molecular and cellular basis of pulmonary vascular remodeling in pulmonary hypertension. Prog Cardiovasc Dis 2002;45:173-202.   DOI
15 Sage E, Mercier O, Van den Eyden F, et al. Endothelial cell apoptosis in chronically obstructed and reperfused pulmonary artery. Respir Res 2008;9:19.   DOI
16 Thomas HC, Lame MW, Dunston SK, Segall HJ, Wilson DW. Monocrotaline pyrrole induces apoptosis in pulmonary artery endothelial cells. Toxicol Appl Pharmacol 1998;151:236-44.   DOI
17 Price LC, Wort SJ, Perros F, et al. Inflammation in pulmonary arterial hypertension. Chest 2012;141:210-21.   DOI
18 Perros F, Dorfmuller P, Souza R, et al. Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension. Eur Respir J 2007;29:462-8.   DOI
19 Stenmark KR, Meyrick B, Galie N, Mooi WJ, McMurtry IF. Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure. Am J Physiol Lung Cell Mol Physiol 2009;297:L1013-32.   DOI
20 Levy M, Maurey C, Celermajer DS, et al. Impaired apoptosis of pulmonary endothelial cells is associated with intimal proliferation and irreversibility of pulmonary hypertension in congenital heart disease. J Am Coll Cardiol 2007;49:803-10.   DOI
21 Han I, Yun M, Kim EO, Kim B, Jung MH, Kim SH. Umbilical cord tissuederived mesenchymal stem cells induce apoptosis in PC-3 prostate cancer cells through activation of JNK and downregulation of PI3K/ AKT signaling. Stem Cell Res Ther 2014;5:54.   DOI
22 Puri MC, Nagy A. Concise review: embryonic stem cells versus induced pluripotent stem cells: the game is on. Stem Cells 2012;30:10-4.   DOI
23 Ohnishi S, Yanagawa B, Tanaka K, et al. Transplantation of mesenchymal stem cells attenuates myocardial injury and dysfunction in a rat model of acute myocarditis. J Mol Cell Cardiol 2007;42:88-97.   DOI
24 Semedo P. Wang PM, Andreucci TH, et al. Mesenchymal stem cells ameliorate tissue damages triggered by renal ischemia and reperfusion injury. Transplant Proc 2007;39:421-3.   DOI
25 Lee H, Lee JC, Kwon JH, et al. The effect of umbilical cord blood derived mesenchymal stem cells in monocrotaline-induced pulmonary artery hypertension rats. J Korean Med Sci 2015;30:576-85.   DOI
26 Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006;24:1294-301.   DOI
27 Hong YM, Kwon JH, Choi S, Kim KC. Apoptosis and inflammation associated gene expressions in monocrotaline-induced pulmonary hypertensive rats after bosentan treatment. Korean Circ J 2014;44:97-104.   DOI
28 Kim KC, Lee HR, Kim SJ, Cho MS, Hong YM. Changes of gene expression after bone marrow cell transfusion in rats with monocrotalineinduced pulmonary hypertension. J Korean Med Sci 2012;27:605-13.   DOI
29 Chu PH, Jung SM,Yeh CH, et al. Expression of caspase-3-dependent apoptosis in mural thrombi leukocytes. APMIS 2008;116;995-9.   DOI
30 Cai J, Jiang WG, Ahmed A, Boulton M. Vascular endothelial growth factor-induced endothelial cell proliferation is regulated by interaction between VEGFR-2, SH-PTP1 and eNOS. Microvasc Res 2006;71:20-31.   DOI