Analysis of the Crosstalk between Myocardium and Vasculature:Mechanism of Prevention of Hypertension by Intervention in Prehypertensive Stage

心肌与脉管系统的串扰分析：高血压前期干预预防高血压的机制

基本信息

批准号：
21590943
负责人：
KAI Hisashi
金额：
$ 2.91万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590943/
关键词：
高血圧心筋細胞血管平滑筋遺伝子発現細胞間クロストーク

项目摘要

We established a selective and comprehensive gene expression pattern analysis separating the myocardium and vasculature in the heart using the laser microdissection(LMD) method. To investigate the effects of pharmacological intervention at the prehypertensive phase on the development of hypertension, an angiotensin II receptor blocker(ARB) was administered to stroke-prone spontaneously hypertensive rats(SHR-SP) of 4-7 weeks old. SHR-SP with early exposure to ARB showed significantly lower blood pressure at hypertensive stage than those without ARB treatment. Also, the incidence of stroke and the incidence of all cause death were significantly lower in SHR-SP with ARB early exposure than those without ARB. The mRNA expression patterns of the myocardium area and vascular area were being compared separately between SHR-SP with and without ARB early exposure. A rat model of a combination of hypertension and large blood pressure variability(BPV) was created by performing a sino-aortic denervation in spoitaneously hypertensive rats. In normotensive rats, increased BPV induced only limited cardiac hypertrophy and fibrosis. In contrast, large BPV exaggerated cardiac hypertrophy and fibrosis, leading to LV systolic dysfunction in SHR. It was reveled that chronic inflammation of the intramyocardial arterioles elicited the large BPV-induced aggravation of cardiac remodeling. The gene expression profile changes induced specifically by a combination of hypertension and large BPV were being investigated separately in the myocardium area and vascular area.

我们使用激光显微解剖（LMD）方法建立了一种选择性且全面的基因表达模式分析，该模式分析了心脏的心肌和脉管系统。为了研究药理学干预在高血压阶段的影响对高血压发展的影响，将血管紧张素II受体阻滞剂（ARB）施用针对4-7周的自发性高血压大鼠（SHR-SPH）。与未经ARB治疗的SHR SH-SP相比，早期暴露于ARB的SHR SH-SP在高血压阶段表现出明显较低的血压。同样，在ARB早期暴露的SHR SPH中，中风的发生率和所有原因的死亡率明显低于没有ARB的死亡。在有和没有ARB早期暴露的SHR-SP中，正在比较心肌区域和血管区域的mRNA表达模式。高血压和大血压变异性（BPV）组合的大鼠模型是通过在副高血压大鼠中进行中亚公式神经来创建的。在正常的大鼠中，增加的BPV仅诱导有限的心肥力和纤维化。相比之下，大BPV夸大了心脏肥大和纤维化，导致SHR的LV收缩功能障碍。人们对心脏内动脉的慢性炎症引起了BPV诱导的大型心脏重塑的加剧。 The gene expression profile changes induced specifically by a combination of hypertension and large BPV were being investigated separately in the myocardium area and vascular area.