Effect and mechanism of cardiosphere-derived cells in the treatment of heart failure with preserved ejection fraction in rats / 中国基层医药

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.