title: Mesenchymal stem cell prevention of vascular remodeling in high flow-induced pulmonary hypertension through a paracrine mechanism.
abstract: Pulmonary arterial hypertension (PAH) is characterized by functional and structural changes in the pulmonary vasculature, and despite the drug treatment that made significant progress, the prognosis of patients with advanced PH remains extremely poor. In the present study, we investigated the early effect of bone marrow mesenchymal stem cells (BMSCs) on experimental high blood flow-induced PAH model rats and discussed the mechanism. BMSCs were isolated, cultured from bone marrow of Sprague-Dawley (SD) rat. The animal model of PAH was created by surgical methods to produce a left-to-right shunt. Following the successful establishment of the PAH model, rats were randomly assigned to three groups (n=20 in each group): sham group (control), PAH group, and BMSC group (received a sublingual vein injection of 1-5 × 10(6) BMSCs). Two weeks after the administration, BMSCs significantly reduced the vascular remodeling, improved the hemodynamic data, and deceased the right ventricle weight ratio to left ventricular plus septal weight (RV/LV+S) (P<0.05). Real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry analysis results indicated that the inflammation factors such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) were reduced (P<0.05); the expression of matrix metallo proteinase-9 (MMP-9) was lower (P<0.05); vascular endothelial growth factor (VEGF) was higher in BMSC group than those in PAH group (P<0.05).
  
  
  CONCLUSIONS
  Sublingual vein injection of BMSCs for 2 weeks, significantly improved the lung and heart injury caused by left-to-right shunt-induced PAH; decreased pulmonary vascular remodeling and inflammation; and enhanced angiogenesis.
authors.affiliation: Central Research Laboratory, The Second Hospital of Shandong University, Jinan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Luan
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Kong
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Cheng
authors.forename: Tong-Gang
authors.initials: TG
authors.lastname: Qi
authors.forename: Zhao-Hua
authors.initials: ZH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006976:Hypertension, Pulmonary / Q000473:pathology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D019899:Paracrine Communication / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines