EXERCISE, DIABETES, & CORONARY SMOOTH MUSCLE Ca2+
锻炼、糖尿病、
基本信息
- 批准号:6630773
- 负责人:
- 金额:$ 38.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-04-01 至 2004-08-31
- 项目状态:已结题
- 来源:
- 关键词:atherosclerotic plaque biological signal transduction blood lipid calcium flux calcium ion confocal scanning microscopy coronary disorder diabetes mellitus dietary lipid electrophysiology endothelin exercise high performance liquid chromatography histology myocardium phosphorylation sarcolemma swine vasomotion voltage /patch clamp
项目摘要
DESCRIPTION (provided by applicant): The long-term goal of this project is to determine the extent to which exercise training decreases coronary artery disease (CAD) after stenting in diabetes and the coronary smooth muscle (CSM) Ca signaling mechanisms involved. We propose that CAD progression in non-stented conduits and/or microvascular dysfunction may contribute to the increased mortality after coronary stenting in diabetes. We have shown that Diabetic Dyslipidemic (DD) pigs have accelerated coronary atheroma, thus making it feasible to stent natural atherosclerotic lesions, not balloon-injured healthy arteries. Overall hypothesis: exercise-induced change in Ca localization is a pivotal signal to attenuate increased growth of conduit CSM and contraction of microvascular CSM after stenting in DD. Overall experimental design: coronary stents are placed in low fat fed healthy controls (C), high fat/cholesterol fed hyperlipidemic and atherosclerotic (H), diabetic dyslipidemic and atherosclerotic (DD), and DD pigs that are aerobically exercise trained (DDX). Specific Aims are to test the hypotheses that in DD, compared to non-diabetics (H), after Iong-ter m recovery from stenting: 1) In-stent restenosis is not increased; instead, progression of CAD in non-stented cohduits and microvascular dysfunction are increased and both are prevented by exercise. Intravascular ultrasound will provide high spatial resolution of in vivo morphology and intravascular Doppler FIoWires will assess microvascular dysfunction. 2) Progression of CAD in non-stented conduits, but not microvascular dysfunction, is directly related to increased coronary endothelin and smooth muscle growth, which are prevented by exercise. Histology will determine the extent of intimal thickening and endothelin content in conduits. HPLC measures of coronary artery lipids will complement histology to determine whether DD have more cellular lesions than H. 3) Progression of CAD in non-stented conduits is directly related to increased tyrosine kinase, Can., and Kca current, which are prevented by exercise. Single cell tyrosine phosphorylation, distribution of Ca stores, and nuclear Ca (Ca/n) will be measured with confocal microscopy. Ca-dependent K currents (Kca) will be measured with patch clamp. 4) Microvascular dysfunction involves no change in Can, but is directly related to decreased Kca current, which is prevented by exercise. Functional Ca release is at the sarcolemma eliciting Kca, hyperpolarization, and relaxation in C, while Kca decreases in DD. Significance of this research is the relation of clinical and functional endpoints (Aims 1,2) to the differences in Ca localization mechanisms (Aims 3,4) of the therapeutic effects of exercise on conduit vs. microvascular CSM in diabetic dyslipidemia.
描述(由申请人提供):本项目的长期目标是确定运动训练在糖尿病支架植入术后降低冠状动脉疾病(CAD)的程度以及涉及的冠状动脉平滑肌(CSM)Ca信号传导机制。 我们认为,非支架导管的CAD进展和/或微血管功能障碍可能导致糖尿病患者冠状动脉支架植入术后死亡率增加。 我们已经证明,糖尿病血脂异常(DD)猪加速了冠状动脉粥样硬化,从而使其可行的支架自然动脉粥样硬化病变,而不是球囊损伤的健康动脉。 总体假设:运动诱导的Ca定位变化是减弱DD支架植入后导管CSM生长和微血管CSM收缩增加的关键信号。 总体实验设计:将冠状动脉支架放置在低脂肪喂养的健康对照(C)、高脂肪/胆固醇喂养的高血脂和动脉粥样硬化(H)、糖尿病血脂异常和动脉粥样硬化(DD)和有氧运动训练的DD猪(DDX)中。 具体目的是检验以下假设:与非糖尿病患者(H)相比,DD患者在支架植入术后较长时间恢复后:1)支架内再狭窄未增加;相反,非支架植入的冠心病进展和微血管功能障碍增加,运动可预防这两种情况。 血管内超声将提供体内形态的高空间分辨率,血管内多普勒FIoWire将评估微血管功能障碍。 2)非支架导管中CAD的进展,而不是微血管功能障碍,与冠状动脉内皮素增加和平滑肌生长直接相关,而运动可以预防这些。 组织学将确定内膜增厚的程度和导管中内皮素的含量。 冠状动脉脂质的HPLC测量将补充组织学,以确定DD是否比H有更多的细胞病变。3)非支架导管中CAD的进展与酪氨酸激酶的增加直接相关,和Kca电流,这是由运动阻止。 将使用共聚焦显微镜测量单细胞酪氨酸磷酸化、Ca储存分布和细胞核Ca(Ca/n)。 将使用膜片钳测量Ca依赖性K电流(Kca)。 4)微血管功能障碍不涉及Can的变化,但与运动预防的Kca电流降低直接相关。 功能性钙释放是在肌膜引发Kca,超极化,并在C松弛,而在DD Kca减少。 本研究的意义在于临床和功能终点(目的1、2)与运动对糖尿病血脂异常中导管与微血管CSM的治疗效果的Ca定位机制(目的3、4)差异的关系。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Michael Sturek其他文献
Michael Sturek的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Michael Sturek', 18)}}的其他基金
Swine Core - Regional/National Shared Resources Core
养猪核心 - 区域/国家共享资源核心
- 批准号:
10155472 - 财政年份:2015
- 资助金额:
$ 38.93万 - 项目类别:
PORCINE MODELS OF CORONARY ARTERY DISEASE IN DIABETES
糖尿病冠状动脉疾病的猪模型
- 批准号:
7621683 - 财政年份:2007
- 资助金额:
$ 38.93万 - 项目类别:
EXERCISE, DIABETES, AND CORONARY SMOOTH MUSCLE CALCIUM
运动、糖尿病和冠状动脉平滑肌钙
- 批准号:
6184686 - 财政年份:1999
- 资助金额:
$ 38.93万 - 项目类别:
EXERCISE, DIABETES, AND CORONARY SMOOTH MUSCLE CALCIUM
运动、糖尿病和冠状动脉平滑肌钙
- 批准号:
6390349 - 财政年份:1999
- 资助金额:
$ 38.93万 - 项目类别:
EXERCISE, DIABETES, AND CORONARY SMOOTH MUSCLE CALCIUM
运动、糖尿病和冠状动脉平滑肌钙
- 批准号:
6537584 - 财政年份:1999
- 资助金额:
$ 38.93万 - 项目类别:
相似海外基金
ROLE OF CELL ADHESION IN BIOLOGICAL SIGNAL TRANSDUCTION
细胞粘附在生物信号转导中的作用
- 批准号:
6238317 - 财政年份:1997
- 资助金额:
$ 38.93万 - 项目类别:
ROLE OF CELL ADHESION IN BIOLOGICAL SIGNAL TRANSDUCTION
细胞粘附在生物信号转导中的作用
- 批准号:
5210031 - 财政年份:
- 资助金额:
$ 38.93万 - 项目类别: