Aging, Estrogen, and Coronary Endothelial Function

衰老、雌激素和冠状动脉内皮功能

• 批准号: 7743909
• 负责人: JUDY M DELP
• 金额: $ 22.46万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-15 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7743909
• 关键词: Adrenergic Agents; Affect; Age; Aging; Aging-Related Process; Animals; Blood Vessels; Blood flow; Cardiac; Cardiac Output; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cause of Death; Coronary; Data; Development; Elderly; Endothelium; Endothelium-Dependent Relaxing Factors; Estrogen Replacements; Estrogens; Excision; Female; Future; Gender; Heart; Heart Rate; Heart failure; Human; Impairment; Individual; Knowledge; Lead; Life; Mediating; Menopause; Messenger RNA; Myocardial; NOS1 protein, human; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Ovarian hormone; Ovariectomy; Pathology; Performance; Pharmacia brand of estropipate; Physiological; Population; Protein Isoforms; Rattus; Regulation; Relative (related person); Research Personnel; Resistance; Risk; Role; Signal Transduction; Site; Stimulus; Stroke Volume; United States; Vascular resistance; Vasodilation; Woman; Work; adrenergic; age effect; age related; aged; arteriole; body system; cardiovascular disorder risk; disorder risk; experience; heart disease risk; human NOS3 protein; human very old age (85+); improved; insight; male; men; middle age; neuroregulation; programs; protein expression; reproductive; response; restoration; senescence

DESCRIPTION (provided by applicant): The risk for heart disease increases dramatically with advancing age. Before the age of menopause, the risk for heart disease in women is reduced compared to that of men; however, after menopause the risk in women increases to a level greater than that of men. Although an age related decrease in coronary blood flow capacity may contribute to the increased risk of heart disease in both males and females, little is known of the interactive effects of age and estrogen on vasoreactivity of the coronary resistance vasculature, the major site for control of coronary blood flow. Recent work indicates that age impairs endothelium-dependent, nitric oxide (NO)-mediated vasodilation of coronary resistance arterioles from both male and female rats; however, preliminary data suggest that the mechanistic changes that result in impaired NO-mediated dilation differ between genders. Therefore, the overall aim of this proposal is to determine the mechanisms by which age and estrogen status alter endothelium dependent, NO-mediated vasodilation in coronary arterioles. Aim 1 is to determine the effect of age and estrogen status on cellular signaling mechanisms that regulate NO-mediated dilation in coronary arterioles. Aim 2 is to determine the effects of age and estrogen status on the contribution of nitric oxide synthase (NOS) isoforms to endothelium-dependent dilation and the activity of (NOS) isoforms in coronary arterioles. Aim 3 is to determine the effects of age and estrogen status on mRNA and protein expression of NOS isoforms in coronary arterioles. These studies will identify mechanisms that contribute to the age-related impairment of NO-mediated vasodilation and determine whether estrogen treatment can improve NO-mediated vasodilation thru restoration of these signaling mechanisms. The information gained from this work will increase our understanding of the effects of age and estrogen in the coronary resistance vasculature and provide insight into the mechanisms that contribute to the age-related loss of endothelial function in both males and females.

描述（由申请人提供）：随着年龄的增长，患心脏病的风险急剧增加。在绝经年龄之前，女性患心脏病的风险比男性低；然而，绝经后，女性的风险会高于男性。 尽管与年龄相关的冠状动脉血流量下降可能会增加男性和女性患心脏病的风险，但人们对年龄和雌激素对冠状动脉阻力脉管系统（控制冠状动脉血流的主要部位）的血管反应性的相互作用的影响知之甚少。最近的研究表明，年龄会损害雄性和雌性大鼠冠状动脉阻力小动脉的内皮依赖性、一氧化氮（NO）介导的血管舒张作用。然而，初步数据表明，导致 NO 介导的扩张受损的机制变化在性别之间存在差异。因此，本提案的总体目标是确定年龄和雌激素状态改变冠状动脉内皮依赖性、NO 介导的血管舒张的机制。目标 1 是确定年龄和雌激素状态对调节 NO 介导的冠状动脉扩张的细胞信号传导机制的影响。 目标 2 是确定年龄和雌激素状态对一氧化氮合酶 (NOS) 亚型对内皮依赖性扩张的贡献以及冠状动脉 (NOS) 亚型活性的影响。 目标 3 是确定年龄和雌激素状态对冠状动脉中 NOS 亚型 mRNA 和蛋白质表达的影响。这些研究将确定导致 NO 介导的血管舒张与年龄相关的损害的机制，并确定雌激素治疗是否可以通过恢复这些信号机制来改善 NO 介导的血管舒张。 从这项工作中获得的信息将增加我们对年龄和雌激素对冠状动脉阻力脉管系统影响的理解，并深入了解导致男性和女性与年龄相关的内皮功能丧失的机制。

项目成果

Effects of age and exercise training on coronary microvascular smooth muscle phenotype and function.

• DOI: 10.1152/japplphysiol.00459.2017
• 发表时间: 2018
• 期刊: Journal of applied physiology
• 影响因子: 3.3
• 作者: J. Muller-Delp;K. Hotta;Bei Chen;B. Behnke;Joshua J. Maraj;M. Delp;Tiffani Lucero;Jeremy A Bramy;David Alarcon;H. Morgan;Morgan Cowan;Anthony Haynes

Redox balance in the aging microcirculation: new friends, new foes, and new clinical directions.

• DOI: 10.1111/j.1549-8719.2011.00139.x
• 发表时间: 2012-01
• 期刊: Microcirculation (New York, N.Y. : 1994)
• 作者: Muller-Delp JM;Gurovich AN;Christou DD;Leeuwenburgh C
• 通讯作者: Leeuwenburgh C

Aging and estrogen status: a possible endothelium-dependent vascular coupling mechanism in bone remodeling.

• DOI: 10.1371/journal.pone.0048564
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Prisby RD;Dominguez JM 2nd;Muller-Delp J;Allen MR;Delp MD
• 通讯作者: Delp MD

Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles.

年龄和运动训练会改变骨骼肌小动脉内皮细胞中活性氧的信号传导。

• DOI: 10.1152/japplphysiol.00341.2012
• 发表时间: 2013
• 期刊: Journal of applied physiology (Bethesda, Md. : 1985)
• 作者: Sindler,AmyL;Reyes,Rafael;Chen,Bei;Ghosh,Payal;Gurovich,AlvaroN;Kang,LoriS;Cardounel,ArturoJ;Delp,MichaelD;Muller-Delp,JudyM
• 通讯作者: Muller-Delp,JudyM