title: Paracrine effects of bone marrow-derived endothelial progenitor cells: cyclooxygenase-2/prostacyclin pathway in pulmonary arterial hypertension.
abstract: BACKGROUND
  Endothelial dysfunction is the pathophysiological characteristic of pulmonary arterial hypertension (PAH). Some paracrine factors secreted by bone marrow-derived endothelial progenitor cells (BMEPCs) have the potential to strengthen endothelial integrity and function. This study investigated whether BMEPCs have the therapeutic potential to improve monocrotaline (MCT)-induced PAH via producing vasoprotective substances in a paracrine fashion.
  
  
  RESULTS
  Bone marrow-derived mononuclear cells were cultured for 7 days to yield BMEPCs. 24 hours or 3 weeks after exposure to BMEPCs in vitro or in vivo, the vascular reactivity, cyclooxygenase-2 (COX-2) expression, prostacyclin (PGI2) and cAMP release in isolated pulmonary arteries were examined respectively. Treatment with BMEPCs could improve the relaxation of pulmonary arteries in MCT-induced PAH and BMEPCs were grafted into the pulmonary bed. The COX-2/prostacyclin synthase (PGIS) and its progenies PGI2/cAMP were found to be significantly increased in BMEPCs treated pulmonary arteries, and this action was reversed by a selective COX-2 inhibitor, NS398. Moreover, the same effect was also observed in conditioned medium obtained from BMEPCs culture.
  
  
  CONCLUSIONS
  Implantation of BMEPCs effectively ameliorates MCT-induced PAH. Factors secreted in a paracrine fashion from BMEPCs promote vasoprotection by increasing the release of PGI2 and level of cAMP.
authors.affiliation: Department of Cardiology, Biomedical Research (Therapy) Center, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Jiang
authors.forename: Jie
authors.initials: J
authors.lastname: Han
authors.forename: Jun-Hui
authors.initials: JH
authors.lastname: Zhu
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Fu
authors.forename: Bin-Quan
authors.initials: BQ
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D011464:Epoprostenol / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000201:enzymology* / Q000473:pathology; D019899:Paracrine Communication; D011651:Pulmonary Artery / Q000201:enzymology / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013234:Stem Cells
chemical_list: D011464:Epoprostenol; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat