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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)
  • Received : 2015.03.30
  • Accepted : 2015.09.15
  • Published : 2016.01.30

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

Acknowledgement

Supported by : The Korean Society of Cardiology, National Research Foundation of Korea

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