Significance of expression of cardiotrophin-1 in remodeled myocardium after acute myocardial infarction in rats

Objective: To study the dynamic changes of cardiotrophin-1(CT-1),mRNA expression in non-infarction zone in left ventricle (LVNIZ) and the relationship between the changes and left ventricular remodeling (LVRM) in rats with AMI, also to evaluate the effect of losartan on CT-1 expression. Method:The 73 surviving acute myocardial infarction(AMI) male Wistar rats were randomly divided into 2 groups at 24 hours after MI: AMI group and losartan treatment group. The former was subdivided into 6 groups according to different time at 1st, 3 rd, 7 th, 14 th, 21 st, 28 th day after AMI. Losartan was delivered by direct gastric gavage (20 mg·kg -1·d -1) for 4 weeks beginning at 2nd after AMI. Sham-operated and normal rats were selected randomly to serve as non-infarcted controls. There are 8 rats in each group. Myocardial AngⅡand collagen contents(HC) were measured by radioimmunoassay and chloramine T method respectively in LVNIZ. CT-1 mRNA expression in LVNIZ was determined by RT-PCR. Result:①Compared with sham-operated rats and control rats, both myocardial AngⅡand HC in LVNIZ were markedly increased (P 0.05~ 0.001) in AMI groups and positively related to LVRM (all P 0.01); ②The expression of CT-1 mRNA in LVNIZ gradually increased as early as 1 day after MI, peaked at 14 day and declined thereafter, but remained higher than those in sham-operated rats (P 0.05~ 0.01); ③Correlation analysis found that there were significant positive correlations among CT-1 mRNA level、myocardial AngⅡ、HC and LVRM (P 0.05~ 0.01);④Myocardial AngⅡ、HC and CT-1 mRNA were all decreased in losartan-treated group with depressed LVRM compared with 28 days after MI group(P 0.05). Conclusion:Overexpression of CT-1 mRNA in LVNIZ may play an important role in LVRM after MI. The mechanisms of losartan in preventing LVRM may be partly through depressing CT-1 transcripition, which is worth studying further.