摘要
Objective To study the role of hypertension-related gene (HRG-1) in cardiovascular disease. Methods The expression of HRG-1 was analyzed with RT-PCR and Northern blotting. Vascular smooth muscle cell (VSMC) proliferation was measured with 3 H-TdR incorporation and was confirmed with histological analysis. Results Northern blot analysis showed that HRG-1 mRNA was expressed not only in VSMC, but also in various rat tissues (heart, brain, lung, kidney, and liver). In addition, the expression of HRG-1 mRNA in heart, brain, kidney and liver of spontaneously hypertensive rat (SHR) was lower than that in the same tissues of Wistar-Kyotorat (WKY). Semi-quantitative RT-PCR and histological analysis showed that the expression of HRG-1 mRNA in ApoE-knockout mice and in animal models of restenosis was decreased and neointimal formation was observed in both models. ET, AII, and IL-1 stimulating VSMC proliferation reduced the expression of HRG-1 mRNA of VSMC. Atrial natriuretic factor (ANF), calcitonin gene-related peptide and adrenomedullin, inhibited VSMC proliferation and elevated the expression of HRG-1 mRNA. These effects could be blocked or attenuated by their corresponding antagonists or antibodies. Conclusion HRG-1 is a gene related to VSMC proliferation. It may play an important role in several occlusive cardiovascular diseases including atherosclerosis, restenosis and hypertension.
目的 研究高血压相关基因 (HRG 1)在心血管病发病中的作用。方法 用RT PCR和Northernblot分析HRG 1的表达。用3 H TdR掺入和组织学方法检测血管平滑肌细胞 (VSMC)的增殖。结果 Northernblot分析显示 ,HRG 1mRNA不仅可在VSMC中表达 ,亦可在大鼠多种组织中表达 (心、脑、肺、肾和肝 )。此外 ,在SHR大鼠的心、脑、肾和肝组织的HRG 1基因表达均明显低于正常WKY大鼠。半定量RT PCR和组织学分析表明 ,ApoE敲除小鼠和再狭窄动物模型的HRG 1mRNA表达减少 ,并且均可见到新生内膜形成。刺激VSMC增殖的ET ,AII和IL 1可减少VSMCHRG 1mRNA的表达。ANF ,CGRP和Adm可抑制VSMC增殖 ,增加HRG 1mRNA表达。这些作用能被相应的阻断剂或抗体所阻断或抑制。结论 HRG 1是一种与VSMC增殖相关的基因 ,它在动脉粥样硬化 ,再狭窄和高血压等心血管疾病中可能具有重要作用。
基金
ThisprojectwassupportedbyNationalNaturalScienceFoundationofChina (No 39870 35 5 )