Effects Of Erythropoietin On Extracellular Matrix Remodeling After Myocardial Infarction In Rats

Objective To observe the effects of recombinant human erythropoietin on cardiac interstitium in rats after the induction of a myocardial infraction by permanent ligation of the left descending coronary artery.To explore the cardio-protective mechanisms of recombinant human erythropoietin.Methods 48 adult male Sprague-Dawley rats were randomly separated into four groups:sham operation group(S group),sham operation and rhEPO group(SE group),operation group(O group),operation and rhEPO group(OE group). Myocardial infraction model was established in the experiments.The model rats were subjected to ligation of the left descending coronary artery.The rats in the SE group and OE group received a single intraperitoneally injection of rhEPO(3000 units/kg in 0.3 ml of saline).Hematocrit,echocardiography,Infarct size,fibrosis and collagen volume fraction were tested. Specimens of the left ventricle were taken for determination of matrix metalloproteinase-2 and matrix metalloproteinase -9 protein and mRNA by immunohistochemistry and RT-PCR.Results (1)The average changes in hematocrit in rats treated with rhEPO did not differ from those receiving saline(P>0.05).The slight increases of hematocrit in EPO-treated rats on days 14 were not statistically significant.(2)Four weeks after myocardial infraction,echocardiography revealed that the left ventricular end-diastolic dimension(LVDd),left ventricular end-systolic dimension(LVDs) , left ventricular end-diastolic volume(LVEDV) and left ventricular end-systolic volume(LVESV) were significantly increased,and left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS) were significantly decreased in O and OE groups compared with those in S and SE groups(P<0.05).LVDd,LVDs,LVEDV,LVESV were significantly higher,while LVEF and LVFS were significantly lower in O group compared with those in OE group(P<0.05).(3)â… ,â…¢collagen volume fraction and ratio were significantly lower in OE group compared with those in O group,â… collagen was decreased most(P<0.05).Infarct size calculated as fractional area of the scar was significantly smaller in rhEPO-treated group than O group(P<0.05).(4)Four weeks after myocardial infraction,the protein expressions of MMP-2 and MMP-9 in O and OE groups were significantly higher than that in S and SE groups(P<0.05),and the protein expressions of MMP-2 and MMP-9 in OE group were lower than that in O group(P<0.05).(5) The mRNA expressions of MMP-2 and MMP-9 in O and OE groups were significantly higher than that in S and SE groups(P<0.05),and the mRNA expressions of MMP-2 and MMP-9 in OE group were lower than that in O group(P<0.05).Conclusion Increased expressions of MMP-2,MMP-9,collagenâ… and collagenâ…¢, interstitial fibrosis and degraded left ventricular function may play an important role in cardiac remodeling following myocardial infarction.Early intervention of rhEPO can decrease interstitial fibrosis and collagen volume, prevent left ventricular remodeling and improve left ventricular function.