The role of Candiotrophin-1 and its receptoi component, rpbi, in the heart.

点击翻译按钮获取中文摘要

Cardiotrophin-1 (CT-1) is a potent cytokine that stimulates the assembly of sarcomeric units in series in cardiomyocytes through gp130 signaling, resulting in myocardial cell hypertrophy. We examined the role of CT-1 and gp130 system in the two rat models of congestive heart failure. TO clarify the role of CT-1 and the gp130-signaling pathway during ventricular remodeling after myocardial infarction. we examined the expression of CT-1 and gp130 in a rat model of myocardial infarction. All animals developed large myocardial infarctions and progressive left ventricular dilatation and inadequate hypertrophy of the surviving myocardium were confirmed by echocardiography. CT-1 and gp130 mRNA levels were determined by semiquantitative RT-PCR followed by Southern blotting. The densitometric analysis of the Southern blots revealed a significant increase in CT-1 and gp130 mRNA levels compared with those of the sham-operated rats at 1, 3, 7, 14, 28 and 56 days post-infarct in the infarct area, t … More he ventricular septum and right ventricle. The protein levels of CT- and gp130, determined by Western blot analysis, were significantly increased compared to those of sham-operated rats, and peaked in the acute stage and declined thereafter in the three regions described above. Immunohistochemical staining showed that CT-1 and gp130-immunoreactivities were detected in cardiomyocytes and fibroblast-like cells and that the intensity of staining was increased at 7days post-infarct compared with that in sham-operated rats. An augmented CT-1 and gp130 system thus seems to play an important role during ventricular remodeling after myocardial infarction. We also determined the expression levels of CT-1 and gp130 during the transition from cardiac hypertrophy to heart failure using Dah1-salt-sensitive rats with hypertension. CT-1 expression was increased in the stage of heart failure, in which we confirmed the assembly of sarcomeric units in series. Thus, CT-1 contributes to the ventricular dilatation by elongating cardiomyocytes. These findings in the two heart failure models strongly suggest that CT-1 plays a central role in the ventricular dilatation in heart failure. Less