Effect and mechanism of cardiosphere-derived cells in the treatment of heart failure with preserved ejection fraction in rats
10.3760/cma.j.issn.1008-6706.2017.16.001
- VernacularTitle:心肌球源性干细胞在射血分数保留的心力衰竭治疗中的作用机制研究
- Author:
Xuefeng TIAN
;
Guijia ZHU
;
Sining LIU
;
Ning LU
;
Yue ZHANG
;
Zheng WANG
- Keywords:
Stem cells;
Heart failure;
Fibrosis;
Rats
- From:
Chinese Journal of Primary Medicine and Pharmacy
2017;24(16):2401-2405,后插1
- CountryChina
- Language:Chinese
-
Abstract:
Objective To test whether cardiosphere-derived cells(CDCs)were sufficient to decrease manifestations of heart failure with preserved ejection fraction(HFpEF)in hypertensive rats.Methods DS rats(Charles River,Wilmington,Massachusetts)were fed 0.3% NaCl(low-salt)diet until 7 weeks of age.At that time,the diet was switched to an 8% NaCl(high-salt)diet in rats by random assignment.DS rats fed the low-salt diet constituted the control group(n=20).At 13 to 14 weeks of age,rats with the high-salt diet were randomized to receive allogeneic rat CDCs or PBS.Echocardiography long-axis images of the left ventricular systolic and diastolic dimensions.Sirius red was used to assess fibrosis and proliferation.Results E/A ratio increased in the PBS-treated group compared with the control group and the CDCs-treated group [(1.20±0.30)vs.(1.70±0.20)or(1.80±0.16),t=0.782,0.844,all P<0.001].LAA kept increasing in the PBS-treated group[(27.20±1.10)mm2 vs.(19.80±0.76)mm2 or(17.80±0.82)mm2,t=0.892,0.774,all P<0.001].The time constant of isovolumic LV pressure fall was prolonged in placebo-treated animals compared with CDCs-treated animals and control rats[(6.2±0.3)×103 mmHg/s vs.(9.4±0.4)×103 mmHg/s,t=0.382,P=0.024;(6.2±0.3)×103 mmHg/s vs.(9.1±0.5)×103 mmHg/s,t=0.883,P=0.022].LVEDP was 2-fold higher in placebo-treated group than in CDC-treated and control animals[(17±10)mmHg vs.(8±3)mmHg,t=0.922,P=0.003;(17±10)mmHg vs.(9±4)mmHg,t=0.922,P=0.004].A dramatic improvement of survival was observed in CDC-treated rats(Kaplan-Meier survival curves)(P=0.027).Cardiac myofibroblasts increased dramatically in PBS-treated(110/field vs.46/field,P<0.001).Inflammatory cytokines expression siginficantly increased in PBS-treated group.Conclusion CDCs improves survival in a rat model of HFpEF through reducing inflammation and fibrosis.
