WHY DO METABOLIC RISK FACTORS CLUSTER WITH HYPERTENSION?

为什么代谢风险因素与高血压密切相关？

基本信息

批准号：
6603737
负责人：
THEODORE W KURTZ
金额：
$ 22.13万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-09-20 至 2005-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6603737
关键词：
animal breeding biotechnology essential hypertension fatty acid metabolism genetic mapping genetic strain genetic susceptibility hyperlipidemia insulin sensitivity /resistance laboratory rat metabolic syndrome spontaneous hypertensive rat

项目摘要

DESCRIPTION: (Adapted from the application) Insulin resistance has been frequently observed in patients with essential hypertension, although the mechanisms responsible for the hypertension "metabolic syndrome" and clustering of cardiovascular risk factors remain poorly understood. Evidence from both family studies and experimental animals indicates that genetic risk factors may play a significant role in the clustering of cardiovascular risk factors. The spontaneously hypertensive rat (SHR), a widely studied experimental animal model of human essential hypertension, also demonstrates increased plasma insulin levels and insulin resistance when compared with other strains with low blood pressure. The PI and her collaborators have derived a novel SHR congenic strain that provides an opportunity to investigate the clustering of hypertension and insulin resistance. By transferring a piece of chromosome 4 from the normotensive Brown Norway rat onto the genetic background of the SHR rat, the applicant has bracketed a specific chromosomal segment approximately 37 cM in size, that improves both blood pressure and insulin resistance in the SHR. This segment also contains the Cd36 gene, which encodes a fatty acid transporter that was previously thought to be a candidate in the pathogenesis of insulin resistance and blood pressure. The PI proposes to use meiotic mapping in an interval specific segregating population to narrowly map the blood pressure locus on chromosome 4, derive a congenic subline that carries the relevant segment of chromosome 4 and test the potential role of Cd36 in blood pressure control and insulin resistance in transgenic SHR by overexpressing this gene.

描述：（从应用程序改编）胰岛素抵抗已经在患有基本高血压的患者中经常观察到，尽管负责高血压“代谢综合征”和聚类的机制心血管危险因素的理解仍然很差。两者的证据家庭研究和实验动物表明遗传危险因素可能在心血管危险因素的聚类中起着重要作用。自发性高血压大鼠（SHR）是一种广泛研究的实验动物人类本质高血压的模型也表明血浆增加与其他低菌株相比，胰岛素水平和胰岛素抵抗血压。 PI和她的合作者得出了一本小说的Shr Compentic 菌株提供了调查聚类的机会高血压和胰岛素抵抗。通过转移一块染色体4 从正常的棕色挪威大鼠到SHR的遗传背景大鼠，申请人将特定的染色体段包围了大约 37厘米的大小，可以提高血压和胰岛素抵抗 shr。该段还包含CD36基因，该基因编码脂肪酸以前被认为是发病机理的候选者的转运蛋白胰岛素抵抗和血压。 PI建议使用减数分裂以间隔特定隔离人群的映射以狭义地绘制染色体上的血压基因座染色体4的相关段并测试CD36的潜在作用转基因SHR中的血压控制和胰岛素耐药性过表达该基因。