title: Mesenchymal stem cells attenuate vascular remodeling in monocrotaline-induced pulmonary hypertension rats.
abstract: Intravenous and intratracheal implantation of mesenchymal stem cells (MSCs) may offer ameliorating effects on pulmonary hypertension (PH) induced by monocrotaline (MCT) in rats. The aim of this study was to examine the anti-remodeling effect of intravenous MSCs (VMSCs) and intratracheal MSCs (TMSCs) in rats with PH, and the underlying mechanisms. MSCs were isolated from rat bone marrow and cultured. PH was induced in rats by intraperitoneal injection of MCT. One week after MCT administration, the rats were divided into 3 groups in terms of different treatments: VMSCs group (intravenous injection of MSCs), TMSCs group (intratracheal injection of MSCs), PH group (no treatment given). Those receiving saline instead of MCT served as negative control (control group). Pulmonary arterial structure was pathologically observed, pulmonary arterial dynamics measured, and remodeling-associated cytokines Smad2 and Smad3 detected in the lungs, three weeks after MCT injection. The results showed that PH group versus control group had higher pulmonary arterial pressure (PAP) and wall thickness index (WTI) 21 days after MCT treatment. The expression of phosphorylated (p)-Smad2 and the ratio of p-Smad2/Smad2 were much higher in PH group than in control group. Fluorescence-labeled MSCs were extensively distributed in rats' lungs in VMSCs and TMSCs groups 3 and 14 days after transplantation, but not found in the media of the pulmonary artery. WTI and PAP were significantly lower in both VMSCs and TMSCs groups than in PH group three weeks after MCT injection. The p-Smad2 expression and the ratio of p-Smad2/Smad2 were obviously reduced in VMSCs and TMSCs groups as compared with those in PH group. In conclusion, both intravenous and intratracheal transplantation of MSCs can attenuate PAP and pulmonary artery remodeling in MCT-induced PH rats, which may be associated with the early suppression of Smad2 phosphorylation via paracrine pathways.
authors.affiliation: Pulmonary-heart Center of Beijing Anzhen Hospital, Capital Medical University, Beijing, 100023, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Xie
authors.affiliation: Cardiovascular Center of Beijing Army General Hospital, Beijing, 100069, China.
authors.forename: Dayi
authors.initials: D
authors.lastname: Hu
authors.affiliation: Cardiovascular Center of Beijing Army General Hospital, Beijing, 100069, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Niu
authors.affiliation: Cardiovascular Center of Beijing Army General Hospital, Beijing, 100069, China.
authors.forename: Suping
authors.initials: S
authors.lastname: Qu
authors.affiliation: Pulmonary-heart Center of Beijing Anzhen Hospital, Capital Medical University, Beijing, 100023, China.
authors.forename: Shenghao
authors.initials: S
authors.lastname: Wang
authors.affiliation: Pulmonary-heart Center of Beijing Anzhen Hospital, Capital Medical University, Beijing, 100023, China. Liushuang_heart@yahoo.cn.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D064752:Atrial Remodeling / Q000187:drug effects / Q000502:physiology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D016686:Monocrotaline / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016686:Monocrotaline