高血压相关基因(HRG-1)在心血管病发病中的作用

摘要

目的研究高血压相关基因(HRG-1)在心血管病发病中的作用。rn方法用RT-PCR和Northern blot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。rn结果 Northern blot分析显示，HRG-1 mRNA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-1 mRNA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VSMC HRG-1 mRNA的表达。ANF, CGRP和Adm可抑制VSMC增殖，增加HRG-1 mRNA表达。这些作用能被相应的阻断剂或抗体所阻断或抑制。rn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。%Objective　To study the role of hypertension-related gene (HRG-1) in cardiovascular disease. rnMethods　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. rnResults　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. rnConclusion　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.