PT  - JOURNAL ARTICLE
AU  - Cheuk-Kwan Sun
AU  - Fan-Yen Lee
AU  - Jiunn-Jye Sheu
AU  - Chun-Man Yuen
AU  - Sarah Chua
AU  - Sheng-Ying Chung
AU  - Han-Tan Chai
AU  - Yen-Ta Chen
AU  - Ying-Hsien Kao
AU  - Li-Teh Chang
AU  - Hon-Kan Yip
TI  - Early Combined Treatment with Cilostazol and Bone Marrow-Derived Endothelial Progenitor Cells Markedly Attenuates Pulmonary Arterial Hypertension in Rats
AID  - 10.1124/jpet.109.154328
DP  - 2009 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 718--726
VI  - 330
IP  - 3
4099  - http://jpet.aspetjournals.org/content/330/3/718.short
4100  - http://jpet.aspetjournals.org/content/330/3/718.full
SO  - J Pharmacol Exp Ther2009 Sep 01; 330
AB  - 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 Sprague-Dawley rats (n = 10/group) were randomized to receive saline injection only (group 1), MCT (70 mg/kg) (group 2), and MCT plus cilostazol (20 mg/kg/day) (group 3), MCT plus BMDEPCs (2.0 × 106 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 was decreased in groups 3 and 4 compared with groups 1 and 5 (all p < 0.05). In addition, mRNA expressions of matrix metalloproteinase-9, tumor necrosis factor-α, and caspase-3 were higher, whereas Bcl-2 and endothelial nitric-oxide synthase were lower in lung and RV in group 2 compared with the other groups (all p < 0.05). The number of alveolar sacs and lung arterioles was lower in group 2 than in other groups and lower in groups 3 and 4 than in group 5 (all p < 0.05). RV systolic pressure (RVSP) and weight were increased in group 2 compared with the 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. The American Society for Pharmacology and Experimental Therapeutics