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实验性高血压对心血管组织中磷酸肌醇水解和原癌基因表达的影响。

Effect of experimental hypertension on phosphoinositide hydrolysis and proto-oncogene expression in cardiovascular tissues.

作者信息

MacIver D H, Green N K, Gammage M D, Durkin H, Izzard A S, Franklyn J A, Heagerty A M

机构信息

Department of Medicine, Withington Hospital, Manchester, UK.

出版信息

J Vasc Res. 1993 Jan-Feb;30(1):13-22. doi: 10.1159/000158970.

DOI:10.1159/000158970
PMID:8435467
Abstract

Products of inositol lipid hydrolysis and levels of c-myc, c-fos and H-ras mRNAs were measured in rat left ventricle and vascular tissues 72 h and 9 days after the induction of aortic coarctation in order to examine inositol phosphate and proto-oncogene signals during the development of pressure-related cardiac and vascular structural changes. There was a significant increase in left ventricular and proximal aortic mass at both time points but no change in mesenteric resistance artery morphology in rats with coarctation. At 72 h there was a significant increase in c-myc, c-fos and H-ras mRNAs in the left ventricle of rats with coarctation, and this was accompanied by increased levels of inositol (1,4,5)-trisphosphate. Similar results were obtained in the proximal but not the distal aorta. In resistance arteries inositol phosphate production and proto-oncogene mRNA expression were unchanged. The results indicate that at 72 h aortic coarctation induced structural thickening in the left ventricle and proximal aorta and was associated with increased inositol phosphate production and stimulation of specific proto-oncogene mRNAs. By 9 days following surgery much of the structural change in these tissues was completed, and these raised cellular signals were no longer observed. The results suggest that both increased inositol lipid hydrolysis and a rise in the expression of these proto-oncogenes are important processes in the development of vascular hypertrophy seen in this model of hypertension.

摘要

在大鼠主动脉缩窄诱导后72小时和9天时,测定其左心室和血管组织中肌醇脂质水解产物以及c-myc、c-fos和H-ras mRNA的水平,以研究压力相关的心脏和血管结构变化发展过程中的肌醇磷酸和原癌基因信号。在这两个时间点,缩窄大鼠的左心室和近端主动脉质量均显著增加,但肠系膜阻力动脉形态无变化。在72小时时,缩窄大鼠左心室中的c-myc、c-fos和H-ras mRNA显著增加,同时伴有肌醇(1,4,5)-三磷酸水平升高。在近端主动脉而非远端主动脉也获得了类似结果。在阻力动脉中,肌醇磷酸生成和原癌基因mRNA表达未发生变化。结果表明,在72小时时,主动脉缩窄诱导左心室和近端主动脉结构增厚,并与肌醇磷酸生成增加和特定原癌基因mRNA的刺激有关。术后9天时,这些组织中的大部分结构变化已完成,且不再观察到这些升高的细胞信号。结果提示,肌醇脂质水解增加和这些原癌基因表达升高都是该高血压模型中所见血管肥大发展过程中的重要过程。

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