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？

• 批准号: 6527239
• 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
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-20 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527239
• 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

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）胰岛素抵抗已经