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肺动脉束带大鼠心脏中基因表达模式的变化

Changing patterns of gene expression in the pulmonary trunk-banded rat heart.

作者信息

LekanneDeprez R H, van den Hoff M J, de Boer P A, Ruijter P M, Maas A A, Chamuleau R A, Lamers W H, Moorman A F

机构信息

Academic Medical Center, University of Amsterdam, Meibergdreef 15, Amsterdam, 1105 AZ, The Netherlands.

出版信息

J Mol Cell Cardiol. 1998 Sep;30(9):1877-88. doi: 10.1006/jmcc.1998.0753.

DOI:10.1006/jmcc.1998.0753
PMID:9769242
Abstract

A pressure-overload model in the rat by banding the pulmonary trunk (PT) was developed to investigate alterations in gene expression in left- and right-ventricular compartments during the transition from compensated right-ventricular (RV) hypertrophy to right heart failure. Right heart failure in rat is characterized by liver cirrhosis, hydrothorax and ascites. The diameter of constriction was found to determine the time course of heart failure development. Only the RV free wall and the right atrium increased in weight, without a difference between compensated and failing RV. An increase in circulating ANP revealed a hypertrophic response of the myocardium, while increased circulating ammonia levels discriminated between compensated hypertrophy and failure. As parameters for stress, fibrosis and Ca2+-handling, changes in the pattern and level of the mRNAs encoding atrial natriuretic peptide (ANP), collagenIIIalpha1, and sarcoplasmic endoplasmic reticular calcium ATPase 2 (SERCA2), phospholamban (PLB) and calsequestrin (CSQ) were studied by Northern blot and in situ hybridization analyses. Pulmonary trunk banding resulted in an induction of ANP mRNA, a moderate increase in collagenIII alpha1 mRNA and a decrease in SERCA2 and PLB mRNA levels in both the left and right ventricles, but changes were most pronounced in the myocardium surrounding the RV cavity. Increased ammonia blood levels are a promising prognostic marker to detect the development of right heart failure.

摘要

通过结扎肺动脉(PT)建立大鼠压力超负荷模型,以研究从代偿性右心室(RV)肥厚转变为右心衰竭过程中左、右心室腔室基因表达的变化。大鼠右心衰竭的特征为肝硬化、胸腔积液和腹水。发现缩窄直径决定心力衰竭发展的时间进程。仅右心室游离壁和右心房重量增加,代偿性和失代偿性右心室之间无差异。循环中ANP增加表明心肌有肥厚反应,而循环中氨水平升高可区分代偿性肥厚和心力衰竭。作为应激、纤维化和钙处理的参数,通过Northern印迹和原位杂交分析研究了编码心房利钠肽(ANP)、Ⅲ型胶原α1、肌浆网/内质网钙ATP酶2(SERCA2)、受磷蛋白(PLB)和肌钙蛋白(CSQ)的mRNA的模式和水平变化。肺动脉结扎导致左、右心室中ANP mRNA诱导、Ⅲ型胶原α1 mRNA适度增加以及SERCA2和PLB mRNA水平降低,但变化在右心室腔周围心肌中最为明显。血氨水平升高是检测右心衰竭发展的一个有前景的预后标志物。

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