| Title | Early Combined Treatment with Cilostazol and Bone Marrow-Derived Endothelial Progenitor Cells Markedly Attenuates Pulmonary Arterial Hypertension in Rats. | | Author(s) | Sun CK, Lee FY, Sheu JJ, Yuen CM, Chua S, Chung SY, Chai HT, Chen YT, Kao YH, Chang LT, Yip HK | | Institution | Chang Gung Memorial Hospital - Kaohsiung Medical Center. | | Source | J Pharmacol Exp Ther 2009 Jun 15. | | Abstract | We investigated whether early combined cilostazol and bone marrow-derived endothelial progenitor cell (BMDEPC) treatment offers synergistic benefit in ameliorating monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. Male Spraque-Dawley rats (n=10 per group) were randomized to receive saline injection only (group 1), MCT (70 mg/kg) (group 2), MCT plus cilostazol (20mg/kg/day) (group 3), MCT plus BMDEPCs (2.0 x 10(6) cells) (group 4), and MCT plus combined cilostazol/BMDEPCs (group 5). Intravenous BMDEPCs and oral cilostazol were given on day 3 after MCT administration. By day 42, connexin43 protein expression in right ventricle (RV) was reduced in group 2 compared with other groups, and also decreased in groups 3 and 4 than in groups 1 and 5 (all p<0.05). Additionally, mRNA expressions of matrix metalloproteinase 9, tumor necrosis factor-alpha, and caspase 3 were higher, whereas Bcl-2 and endothelial nitric oxide synthase were lower in lung and RV in group 2 than in other groups (all p<0.05). Number of alveolar sacs and lung arterioles were lower in group 2 than in other groups, and in groups 3 and 4 than in group 5 (all p<0.05). RV systolic pressure (RVSP) and weight were increased in group 2 than in other groups (all p<0.0001). Moreover, RVSP and RV-to-left ventricle plus septum weight ratio were higher in groups 3 and 4 than in groups 1 and 5 (p<0.001) but showed no difference between groups 1 and 5. In conclusion, early combined autologous BMDEPC/cilostazol treatment is superior to BMDEPC or cilostazol only for preventing MCT-induced PAH. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19528354 |
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