EFFECT OF VASCULAR DISTENSIBILITY ON ENDOTHELIAL DEPENDENT VASOREACTIVITY

血管扩张性对内皮依赖性血管反应性的影响

• 批准号: 7378846
• 负责人: Susan J Zieman
• 金额: $ 0.07万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378846
• 关键词: EFFECT; VASCULAR; DISTENSIBILITY; ENDOTHELIAL; DEPENDENT

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The physiologic changes that render age the most significant risk factor for cardiovascular (CV) disease are unclear. Although increased arterial stiffness and endothelial dysfunction accompany aging and are associated with increased CV risk, the mechanisms by which they impart increased CV risk, and the causal direction of the stiffness/endothelial function relationship are unknown. The recent development of novel agents which increase vascular distensibility (VD) by altering structural components of the vessel wall now allows exploration of these relationships. The guiding hypothesis of this proposal is that increased arterial stiffness itself impairs endothelial function and that an intervention which increases vascular distensibility will improve endothelial function. Specific Aim 1 tests whether decreased VD is associated with impaired endothelial flow-mediated vasodilation (FMD) in the arteries of healthy volunteers. Specific Aim 2 tests whether the endothelial vasoactive response to increased pulsatility following lower limb exercise is diminished in arteries with reduced distensibility. Specific Aim 3 tests the hypothesis that increasing VD improves FMD and exercise-induced pulse perfusion-mediated vasodilation (PPMV) in individuals with increased vascular stiffness. A novel advanced glycation end-product crosslink breaker will be tested in a phase 2a, open label, single-blind, two month treatment comparison investigating the effect of increased VD on endothelial function (FMD at rest and exercise-induced PPMV). The overall goal is to identify a novel, important mechanism whereby vascular stiffening contributes to atherosclerotic risk, and thereby target efforts to reduce this risk by enhancing vascular distensibility.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。使年龄成为心血管（CV）疾病最显著风险因素的生理变化尚不清楚。尽管动脉僵硬度增加和内皮功能障碍伴随衰老，并与CV风险增加相关，但其导致CV风险增加的机制以及僵硬度/内皮功能关系的因果方向尚不清楚。最近开发的通过改变血管壁的结构成分来增加血管扩张性（VD）的新药物现在允许探索这些关系。 该建议的指导假设是，动脉硬度增加本身会损害内皮功能，增加血管扩张性的干预措施将改善内皮功能。具体目标1测试VD降低是否与健康志愿者动脉中内皮血流介导的血管舒张（FMD）受损相关。特定目标2测试下肢运动后血管内皮对脉动性增加的反应是否在扩张性降低的动脉中减弱。具体目标3检验了以下假设：在血管硬度增加的个体中，增加VD可改善FMD和运动诱导的脉冲灌注介导的血管舒张（PPMV）。将在一项2a期、开放标签、单盲、2个月治疗比较中测试一种新型晚期糖基化终产物交联破坏剂，研究VD增加对内皮功能（静息时FMD和运动诱导PPMV）的影响。总的目标是确定一种新的，重要的机制，血管硬化有助于动脉粥样硬化的风险，从而有针对性的努力，以减少这种风险，通过提高血管扩张性。