Experimental Study On Effects And Mechanisms Of Aliskiren On Ventricular Remodeling And Heart Function In Rats Of AMI

Objective:The aim of the study was to investigate the effect and mechanism ofaliskiren on ventricular remodeling and heart function in the rats of acute myocardialinfarction.Methods:60male8-week-old Wistar rats were enrolled and fed in standardenvironment. After one week, they were randomly divided into four groups (n=15, pergroup): sham operated group, control group, perindopril group and aliskiren group. Therats in control group, perindopril group and aliskiren group were all ligated the anteriordescending coronary branch for developing an animal model of anterior myocardialinfarction. Meanwhile, sham operated group was regarded as a concurrent group and therats were subjected to sham coronary ligature. The next day of the operation, the rats inperindopril group and aliskiren group were dosed orally per day with perindopril(2.5mg/kg/d)or aliskiren(50mg/kg/d)for8weeks, respectively. At the same time, theanimals in sham operated group, control group were provided with0.9%saline. Wedetected the parameters as follows:(1) Before and at the end of the experiment, all the ratswere weighed and the blood pressure were assayed.(2) Echocardiographic images wereacquired before and at the end of the experiment. The left ventricular internal diameter atend-diastole(LVIDd),left ventricular internal diameter at end-systole(LVIDs),interventricular septum thickness at end-diastole(IVSd), left ventricle posterior wall atenddiastole(LVPWd), left ventricle ejection fration (LVEF), fractional shortening (FS), theearly diastolic (E), late diastolic (A) velocities and E/A of atrioventricular valve weremeasured.(3)The rats were killed and the samples were obtained. The weight of heart and left ventricle were measured, cardiac mass index (CMI) and left ventricular mass index(LVMI) were calculated too; The myocardial histopathological changes were assayed;ELISA assayed the concentration of hs-CRP in serum; Immunohistochemistry detected theexpression of MMP-2,MMP-9,TIMP-1and TGF-β; RT-PCR determined the mRNAexpression of MMP-2,MMP-9,TIMP-1,TGF-β,Collagen I and III; Western blotdetermined the the protein expression of MMP-2,MMP-9,TIMP-1,TGF-β.Results:1.The total of52rats were survived after the study. The rats were among thegroups as follow:15in sham group,12in control group,12in perindopril group and13inaliskiren group.2. The rats in sham operated group displayed normal echocardiographic images. Therats in control group showed the worsened of left ventricular. Compared to sham operatedgroup, the values of CMI, LVMI, LVIDd and LVIDs were significantly increased, andIVSd,LVPWd,LVEF,FS,E/A were significantly decreased (P＜0.05). In comparisionwith control group, CMI, LVMI, LVIDd and LVIDs were significantly decreased, andIVSd,LVPWd,LVEF,FS,E/A were significantly increased (P＜0.05). So, the disfunctionwas reversed in perindopril group and aliskiren group.3.The value of CVF was higher in control group, perindopril group and aliskirengroup than that in sham operated group (P＜0.05). The value of CVF was lower inperindopril group and aliskiren group than that in control group (P＜0.05). There was nodifference between perindopril group and aliskiren group (P＞0.05).4. The concentration of hs-CRP was higher in control group, perindopril group andaliskiren group than that in sham operated group (P＜0.05). hs-CRP concentration waslower in perindopril group and aliskiren group than that in control group (P＜0.05). Therewas no difference between perindopril group and aliskiren group (P＞0.05).5. The mRNA expressions of MMP-2,MMP-9,TGF-β,Collagen I and III wasupregulated in control group, perindopril group and aliskiren group compared to that insham operated group (P＜0.05). Meanwhile, the mRNA expressions of TIMP-1wasdownregulated in control group, perindopril group and aliskiren group compared to that in sham operated group (P＜0.05). MMP-2,MMP-9,TGF-β,Collagen I and III mRNAexpressions was lower in perindopril group and aliskiren group than that in control group(P＜0.05), and TIMP-1mRNA expressions was higher in perindopril group and aliskirengroup than control group (P＜0.05). There was no difference between perindopril groupand aliskiren group (P＞0.05).6. The protein expressions of MMP-2,MMP-9and TGF-β was upregulated in controlgroup, perindopril group and aliskiren group compared to that in sham operated group (P＜0.05). Meanwhile, protein expressions of TIMP-1was downregulated in control group,perindopril group and aliskiren group compared to that in sham operated group (P＜0.05).MMP-2,MMP-9and TGF-β protein expressions was lower in perindopril group andaliskiren group than that in control group (P＜0.05), and TIMP-1protein expressions washigher in perindopril group and aliskiren group than control group (P＜0.05). There was nodifference between perindopril group and aliskiren group (P＞0.05).Conclusion:1. Aliskiren had a protective effect on ventricular remodeling and cardiac function inthe rats with AMI.2. Aliskiren downregulated the expression of MMP-2, MMP-9,TGF-β,Collagen I, IIIand hs-CRP, upregulated the levels of TIMP-1.3. There was no difference of perindopril and aliskiren treatment on the beneficialeffect of ventricular remodeling and heart function in rats of AMI.