Fath K A, Alexander R W, Delafontaine P
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322.
Circ Res. 1993 Feb;72(2):271-7. doi: 10.1161/01.res.72.2.271.
We have previously demonstrated specific insulin-like growth factor I (IGF I) mRNA transcripts in cultured endothelial and vascular smooth muscle cells and postulated an important role for IGF I in blood vessel growth responses. The purpose of this study was to characterize IGF I gene expression in a model of aortic coarctation hypertension in the rat. This high-renin model of hypertension is associated with hyperplastic vascular responses. Northern analysis of rat aorta demonstrated four specific IGF I mRNA transcripts sized 7.6, 4.6, 1.8, and 0.9-1.2 kb. Quantitation of aortic IGF I mRNA levels by solution hybridization/RNase protection assay demonstrated induction of IGF I transcripts in the hypertensive aorta; levels more than doubled at 7 days and were still significantly elevated 21 days after coarctation. In situ hybridization analysis indicated that IGF I transcripts were localized primarily to adventitial surfaces in normotensive aorta, with minimal signal detected over vascular cells. In hypertensive aortas, there was an increase in IGF I transcripts primarily over vascular smooth muscle cells. Thus, vascular IGF I gene expression is induced in this model of high-renin hypertension. IGF I may play an important role in autocrine/paracrine-mediated vessel wall remodeling in hypertension.
我们之前已在培养的内皮细胞和血管平滑肌细胞中证实了特异性胰岛素样生长因子I(IGF I)mRNA转录本,并推测IGF I在血管生长反应中起重要作用。本研究的目的是在大鼠主动脉缩窄型高血压模型中表征IGF I基因表达。这种高肾素型高血压模型与增生性血管反应相关。对大鼠主动脉进行的Northern分析显示有四种特异性IGF I mRNA转录本,大小分别为7.6、4.6、1.8和0.9 - 1.2 kb。通过溶液杂交/核糖核酸酶保护分析对主动脉IGF I mRNA水平进行定量,结果显示高血压主动脉中IGF I转录本被诱导;缩窄后7天水平增加了一倍多,并且在21天时仍显著升高。原位杂交分析表明,在正常血压的主动脉中,IGF I转录本主要定位于外膜表面,在血管细胞上检测到的信号极少。在高血压主动脉中,IGF I转录本主要在血管平滑肌细胞上增加。因此,在这种高肾素型高血压模型中血管IGF I基因表达被诱导。IGF I可能在高血压中自分泌/旁分泌介导的血管壁重塑中起重要作用。