INSULIN RESISTANCE AND CARDIOVASCULAR RISK FACTORS

胰岛素抵抗和心血管风险因素

基本信息

批准号：
6786649
负责人：
BRENT M EGAN
金额：
$ 14.92万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
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：
2000-09-15 至 2006-08-31
项目状态：
已结题

项目摘要

This K-24 application includes a mentoring plan and two research components which are linked together by the common theme of insulin resistance and cardiovascular risk factor clustering. In part 1 of the research plan, we plan to continue work under the current R01 and a subsequent competitive renewal to test the hypothesis that fatty acids and angiotensin induce a synergistic enhancement of oxidative stress in humans. The three specific aims are to determine (1) the effects of raising fatty acids and angiotensin singly and in combination on markers of platelet PKC activity and oxidative stress (2) the effects of a low NaCl diet, which raises plasma angiotensin II, on markers of oxidative stress in obese hypertensive patients during treatment, with an AT1 receptor antagonist compared to placebo 3) which protein kinase C (PKC) isoform isoform(s) are stimulated by oleic acid and lead to the generation of reactive oxygen species and activation of extracellular signal-regulated kinases in human aortic smooth muscle cells by using antisense oligonucleotides to specific PKCs. Each of these specific aims will be addressed using methods which are well established in our patient-oriented clinical and bench research. In part 2, with the support of this K-24 Award, we plan to extend the generalizability of our findings to the wider community and by addressing important gaps in the literature on low birth weight and cardiovascular risk. We will test the hypothesis that low birth weight contributes to cardiovascular risk and salt sensitivity in a biracial sample of young adults at two college campuses in South Carolina. Three specific aims will be addressed to determine the relationships of low birth weight (<2500 grams) to (1) metabolic components of insulin resistance (oral glucose tolerance test and dyslipidemia (NMR lipid profile) (2) hemodynamic components of the insulin resistance syndrome including laboratory and 24-hour ambulatory blood pressure (BP), baroreflex sensitivity (cross spectral analysis of systolic BP and heart rate), proximal and distal arterial compliance (HDI pulse-wave) and post-ischemic forearm vascular resistance (venous occlusion plethysmography). (3) Salt sensitivity defined by the differences in BP on 180 vs. 80 mmol/d NaCl diets. All of the mentoring activities, which would be supported by the K-24 Award, also relate to various facets of the insulin resistance syndrome. "Access to excess" calories and labor saving devices has produced an epidemic of obesity and cardiovascular risk factors related to insulin resistance. While lifestyle changes are important and the PI and his colleagues work diligently in this area most people are unable to normalize their risk through lifestyle changes alone. We believe that a better definition of the pathophysiological common denominators and key intracellular signaling events mediating these effects will provide the basis for novel therapeutic approaches to cardiovascular disease prevention.

该K-24应用程序包括一个指导计划和两个研究组件，它们通过胰岛素抵抗和心血管危险因素聚类的共同主题联系在一起。在研究计划的第1部分中，我们计划在当前R01下继续工作，并随后具有竞争性更新，以检验以下假设：脂肪酸和血管紧张素会引起人类氧化应激的协同增强。这三个具体目的是确定（1）单独升高脂肪酸和血管紧张素以及对血小板PKC活性和氧化应激的标记的影响（2）低NaCl饮食的影响，降低了血浆血管素II的降低血管蛋白II，对氧化应激标记对肥胖患者的氧化应激标记，在肥胖的患者中，与AT1接收器抗At portor抗体3相比（per ant pork）pert artc and pert artc and artc and artc artc ant。通过油酸刺激同工型（S），导致活性氧的产生，并通过使用反义寡核苷酸对特定的PKCS进行人主动脉平滑肌细胞中细胞外信号调节激酶的激活。这些特定目标将使用在我们以患者为导向的临床和台式研究中确定的方法来解决。在第2部分中，在该K-24奖的支持下，我们计划将发现的普遍性扩展到更广泛的社区，并通过解决有关低出生体重和心血管风险的文献中的重要差距。我们将检验以下假设：在南卡罗来纳州的两个大学校园的年轻人样本中，低出生体重有助于心血管风险和盐敏感性。 Three specific aims will be addressed to determine the relationships of low birth weight (<2500 grams) to (1) metabolic components of insulin resistance (oral glucose tolerance test and dyslipidemia (NMR lipid profile) (2) hemodynamic components of the insulin resistance syndrome including laboratory and 24-hour ambulatory blood pressure (BP), baroreflex sensitivity (cross spectral analysis of收缩的BP和心率），近端和远端动脉依从性（HDI脉冲波）和缺血后的前臂耐药性（静脉闭塞体积图）（3）由180 vs. 80 Mmol/D NaCl Diets的BP差异定义。胰岛素抵抗综合症。我们认为，更好地定义了病理生理的共同点和介导这些作用的关键细胞内信号传导事件将为预防心血管疾病的新型治疗方法提供基础。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cardiovascular risk factor control and treatment patterns in primary care.

初级保健中的心血管危险因素控制和治疗模式。

DOI：
发表时间：
2003
期刊：
Managed care interface
影响因子：
0
作者：
Hendrix,KatharineH;Lackland,DanielT;Egan,BrentM
通讯作者：
Egan,BrentM

Controlling blood pressure in 50% of all hypertensive patients: An achievable goal in the healthy people 2010 report?

DOI：
10.1136/jim-51-06-34
发表时间：
2003-11-01
期刊：
JOURNAL OF INVESTIGATIVE MEDICINE
影响因子：
2.6
作者：
Egan, BM;Basile, JN
通讯作者：
Basile, JN

Concordance between self-reported heights and weights and current and ideal body images in young adult African American men and women.

非洲裔美国年轻男性和女性自我报告的身高和体重与当前和理想身体形象之间的一致性。

DOI：
发表时间：
2007
期刊：
Ethnicity & disease
影响因子：
3.2
作者：
Gilliard,TheodoshaS;Lackland,DanielT;Mountford,WilliamK;Egan,BrentM
通讯作者：
Egan,BrentM

Ethnic differences in the treatment and control of hypertension in patients with diabetes.

糖尿病患者高血压治疗和控制的种族差异。

DOI：
10.1111/j.1524-6175.2005.04542.x
发表时间：
2005
期刊：
Journal of clinical hypertension (Greenwich, Conn.)
影响因子：
0
作者：
Riehle,JessicaFlynn;Lackland,DanielT;Okonofua,EniC;Hendrix,KatherineH;Egan,BrentM
通讯作者：
Egan,BrentM

A systematic approach to managing hypertension and the metabolic syndrome in primary care.

初级保健中管理高血压和代谢综合征的系统方法。