The Effect Of Fluvastatin On Vascular Endothelium And Cardiac Function And Mechanism

ObjectiveTo study the effect of fluvastatin on cardiac remodeling and cardiac function throughheart failure rats model, and to investigate whether fluvastatin could protect endothelialcells. And investigate the possible mechanisms.MethodCHF model was induced by doxorubicin and rats were randomly divided into heartfailure group (n=10) and fluvastatin group (n=10). Another normal10rats served as thecontrol group. Fluvastatin group were treated with fluvastatin (20mg/kg/d),heart failuregroup and control group were treated with normal saline.After6weeks treatment,measured the body weight, left ventricular weight and calculate left ventricular weightindex, measured right ventricular weight and calculate right ventricular weight index.Echocardiographic measured left ventricular end diastolic diameter (LVEDD), leftventricular end systolic diameter (LVESD) and left ventricular ejection fraction (LVEF);the serum levels of ET-1and VWF were measured by enzyme linked immunosorbent assay（ELISA）,the serum levels of ET-1mRNA and VWF mRNA were measured by ReverseTranscription Polymerase Chain Reaction（RT-PCR）.Results（1）Mortality rate of heart failure control group and drug groups were higher than thecontrol group, and mortality rate of drug group were lower than heart failure group.(2)Compared with the control group, Left ventricular end diastolic diameter（LVEDD）, Leftventricular end systolic diameter(LVESD), Left Ventricular Relative Weight(LVRW)andRight Ventricular Relative Weight (RVRW) were significant increased in the heart failurecontrol group and drug group, while LVEF and Left Ventricular Fractional Shortening(LVFS) were significant decreased in the heart failure control group and drug group, but ET-1mRNA and VWF mRNA were significant increased in the Heart failure control groupand drug group.(3) Compared with the heart failure control group, LVEDD,LVESD,LVRW and RVRW were significant decreased in the drug group, while LVEF and LVFSwere significant increased in the drug group,but ET-1mRNA and VWF mRNA weresignificant decreased in the drug group.(4) The level of ET-1was correlated positively withthe level of VWF, while the level of ET-1and VWF were negative correction with theLVEF.Conclusion(1) In CHF rats, the levels of ET-1and VWF in the blood and cardiac issue weresignificantly increased, and ventricular weight index were also increased, and the cardiacremodeled markly and the cardiac function decreased severely.(2) Fluvastatin couldimprove the cardiac function and prevent the cardiac remodeling, the mechanisms may beby reducing the levels of ET-1and VWF and improving endothelial function.