Screening for candidate genes involves in essential hypertension

对于高血压的研究，自发性高血压大鼠(SHR)和卒中易感自发性高血压大鼠(SHRSP)被证明是有价值的模型。在本研究中，我们应用荧光差异显示方法对SHR、SHRSP及其亲本系Wistar京都大鼠(WKY)的主动脉mRNAs进行了筛选，发现了一个在高血压大鼠中持续上调的基因。核苷酸序列测定表明，该基因是大鼠Cyr61的同源基因。Northern印迹分析显示，在高血压发病前，SHR和SHRSP中cyr61的表达增加，此后维持在比年龄匹配的WKY更高的水平。原位杂交结果显示，在高血压大鼠主动脉中膜细胞中，Cyr61有较强的表达，在外膜成纤维细胞中有微弱表达，而在WKY中仅在成纤维细胞中有表达。荧光原位杂交将cyr61基因定位于大鼠染色体1p12-13，该基因此前未被报道为调节血压的数量性状基因座。这些结果表明，Cyr61是一个额外的因子，可能参与了系统性高血压的发生。

For the study of essential hypertension, spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP) have proven to be valuable models. In the present study, we applied a fluorescent differential display method to mRNAs from aortae of SHR, SHRSP and their parental strain, Wistar Kyoto rats (WKY) towards identifying the genes involved in the development of the hypertension, and came across a gene which is consistently upregulated in the hypertensive rats. Nucleotide sequence determination of the corresponding cDNA revealed that the gene is the rat orthologue of cyr61. Northern blot analysis showed that cyr61 expression increases in SHR and SHRSP before the onset of hypertension, and is sustained thereafter at higher levels than in age-matched WKY. In situ hybridization analysis demonstrated that cyr61 is expressed strongly in smooth muscle cells in media, and faintly in fibroblasts in adventitia, of the hypertensive rat aorta, while in WKY the expression is only in fibroblasts. Fluorescent in situ hybridization mapped the cyr61 gene to rat chromosome 1p12-13, which has not been previously reported as a quantitative trait locus for blood pressure regulation. These results suggest that cyr61 is an additional factor which may be involved in the development of systemic hypertension.