权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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：（改编自应用程序）胰岛素抵抗已被在原发性高血压患者中经常观察到，机制负责高血压“代谢综合征”和集群心血管疾病的危险因素仍然知之甚少。双方的证据家庭研究和实验动物表明，遗传风险因素可能在心血管危险因素聚集中起重要作用。自发性高血压大鼠（SHR）是一种被广泛研究的实验动物人原发性高血压模型，也表明血浆中胰岛素水平和胰岛素抵抗与其他菌株相比，血压. PI和她的合作者已经推导出一种新的SHR同源基因菌株，提供了一个机会，调查集群的高血压和胰岛素抵抗。通过转移一段4号染色体从血压正常的布朗挪威大鼠到SHR的遗传背景在大鼠中，申请人将特定的染色体片段括起来， 37厘米的大小，这改善了血压和胰岛素抵抗， SHR。该片段还包含Cd36基因，其编码脂肪酸转运蛋白，以前被认为是一个候选人在发病机制胰岛素抵抗和血压的关系。PI建议使用减数分裂在区间特异性分离群体中作图， 4号染色体上的血压位点，衍生出一个携带 4号染色体的相关片段，并测试Cd36在转基因SHR的血压控制和胰岛素抵抗过度表达这个基因。