Angiotensin II sensitivity, vascular dysfunction and prior preeclampsia
血管紧张素 II 敏感性、血管功能障碍和先兆子痫
基本信息
- 批准号:8916215
- 负责人:
- 金额:$ 62.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-09-15 至 2017-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdrenal GlandsAldosteroneAngiotensin IIAngiotensin ReceptorAntibodiesBlood PressureBlood VesselsCardiovascular DiseasesCellsClinicalClinical TrialsDataDevelopmentDietDietary SodiumDiseaseEndotheliumEquilibriumExcretory functionFutureGoalsHealthHypertensionImmunoglobulin GIn VitroIndividualInfusion proceduresIntakeInterventionIntravenousKidneyLeadMeasurementMeasuresMediatingMediator of activation proteinPeripheral Blood Mononuclear CellPilot ProjectsPlasmaPopulationPre-EclampsiaPregnancyPremenopauseProteinsReceptor ActivationReceptor, Angiotensin, Type 1Recording of previous eventsRelative (related person)Renal Blood FlowRiskRisk FactorsSodiumSodium ChlorideStagingTestingVascular DiseasesVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth FactorsVasodilationWomanbasecardiovascular disorder riskcardiovascular risk factorhuman studyin vivoinsightnormotensivenovelpreventreceptorreceptor sensitivityrenal arteryresponseurinaryvasoconstriction
项目摘要
DESCRIPTION (provided by applicant): A history of preeclampsia is a risk factor for cardiovascular disease (CVD), but the mechanism mediating the increased CVD risk is unknown. Our preliminary results have demonstrated increased angiotensin II (Ang II) sensitivity and salt sensitivity of blood pressure in women with prior hypertensive pregnancy. Thus, this proposal hypothesizes that Ang II sensitivity is mediated by Ang II Type 1 Receptor (AT1R) Activation which Is a Key Mechanistic Factor Leading to Both Vascular Dysfunction and Salt Sensitivity of Blood Pressure, Leading to Future Development of Hypertension and Increased CVD Risk in Women with a History of Preeclampsia. We will test this hypothesis through the following three specific aims: 1) To test the hypothesis that in women with a history of preeclampsia, AT1R activation is associated with vascular dysfunction manifesting as increased Ang II pressor sensitivity and impaired endothelial dependent vasodilation and that AT1R blockade corrects the vascular dysfunction; 2) To test the hypothesis that women with a history of preeclampsia have excess AT1R activity in the kidney leading to impaired ability to augment renal blood flow in response to dietary sodium and in the adrenal leading to increased aldosterone secretion (both correctable by AT1R blockade) and impaired ability to excrete a sodium load, all of which lead to salt sensitivity of blood pressure; 3) To test the hypothesis tha the increased AT1R activity will be explained by alterations in AT1R and/or AT2R level or responsiveness as determined in peripheral blood mononuclear cells obtained from women studied in SAs 1-2. Women with a history of preeclampsia will be studied 1-5 years after pregnancy and compared to women with prior normotensive pregnancy. This proposal will provide insight into the mechanism by which women with a history of preeclampsia are at increased risk for hypertension and CVD, and importantly will set the stage for a clinical trial of
blockade of the AT1R to prevent future CVD in women with a history of preeclampsia.
描述(由申请人提供):子痫病史是心血管疾病(CVD)的危险因素,但是介导CVD风险增加的机制尚不清楚。我们的初步结果表明,血管紧张素II(ANG II)的敏感性和盐敏感性对先前高血压妊娠的女性的血压敏感性增加。因此,该提案假设ANG II敏感性是由ANG II 1型受体(AT1R)激活介导的,这是导致血压血管功能障碍和盐灵敏度的关键机制因素,从而导致高血压的未来发展和患有前丙酸率史的女性CVD风险增加。我们将通过以下三个特定目的来检验这一假设:1)检验以下假设:在具有先兆子痫病史的女性中,AT1R激活与血管功能障碍相关,表现为ANG II施加敏感性和受损的内皮血管舒张性并且AT1R阻断的良好性较高,而AT1R则纠正了AT1R的良好性。 2) To test the hypothesis that women with a history of preeclampsia have excess AT1R activity in the kidney leading to impaired ability to augment renal blood flow in response to dietary sodium and in the adrenal leading to increased aldosterone secretion (both correctable by AT1R blockade) and impaired ability to excrete a sodium load, all of which lead to salt sensitivity of blood pressure; 3)为了检验假设,AT1R活性的增加将通过AT1R和/或AT2R水平的改变或反应性来解释,或在外周血血液单核细胞中确定的,从SAS 1-2中研究的妇女获得。具有先兆子痫史的妇女将在怀孕1 - 5年后与先前怀孕正常的妇女进行研究。该提案将洞悉具有先兆子痫病史的妇女的高血压风险和CVD的风险增加,重要的是,重要的是,将为临床试验奠定基础
封锁AT1R,以防止具有先兆子痫史的妇女的未来CVD。
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 }}
Ellen W Seely其他文献
General practitioners' knowledge about pregnancy complications associated with long-term cardiovascular risk.
全科医生对与长期心血管风险相关的妊娠并发症的了解。
- DOI:
10.24875/gmm.20000064 - 发表时间:
2021 - 期刊:
- 影响因子:0.8
- 作者:
M. Lumbreras;M. A. D. L. Torre;J. L. Hernández;Louise Wilkins;Ellen W Seely - 通讯作者:
Ellen W Seely
Guidelines Guidelines for the Development of Comprehensive Care Centers for Congenital Adrenal Hyperplasia: Guidance from the CARES Foundation Initiative
先天性肾上腺增生症综合护理中心发展指南:CARES 基金会倡议的指导
- DOI:
- 发表时间:
2011 - 期刊:
- 影响因子:0
- 作者:
R. Auchus;S. F. Witchel;Kelly R. Leight;Javier Aisenberg;Ricardo Azziz;T. Bachega;Linda A. Baker;Arlene B. Baratz;Laurence S. Baskin;Sheri A. Berenbaum;D. T. Breault;B. Cerame;Gerard S. Conway;Erica A. Eugster;Stephanie Fracassa;J. Gearhart;Mitchell E. Geffner;K. Harris;Richard S. Hurwitz;A. Katz;Brinda N. Kalro;Peter A. Lee;Gretchen Alger Lin;Karen J. Loechner;Ian Marshall;Deborah P. Merke;C. Migeon;Walter L. Miller;Tamara L. Nenadovich;Sharon E. Oberfield;K. Pass;D. Poppas;M. Lloyd;C. Quigley;F. Riepe;Richard C. Rink;S. Rivkees;David E Sandberg;Traci L. Schaeffer;R. Schlussel;F. Schneck;Ellen W Seely;Diane Snyder;Phyllis W. Speiser;B. Therrell;C. VanRyzin;M. Vogiatzi;M. Wajnrajch;Perrin C. White;Alan E. Zuckerman - 通讯作者:
Alan E. Zuckerman
Safety of GLP-1 Receptor Agonists and Other Second-Line Antidiabetics in Early Pregnancy
GLP-1 受体激动剂和其他二线抗糖尿病药物在妊娠早期的安全性
- DOI:
10.1001/jamainternmed.2023.6663 - 发表时间:
2023 - 期刊:
- 影响因子:39
- 作者:
C. Cesta;Ran S Rotem;B. T. Bateman;Gabriel Chodick;Jacqueline M. Cohen;Kari Furu;M. Gissler;K. Huybrechts;L. Kjerpeseth;M. Leinonen;Laura Pazzagli;H. Zoega;Ellen W Seely;Elisabetta Patorno;S. Hernández - 通讯作者:
S. Hernández
Cardiology patient page. Chronic hypertension in pregnancy.
心脏病学患者页面。
- DOI:
10.1161/circulationaha.106.636472 - 发表时间:
2007 - 期刊:
- 影响因子:37.8
- 作者:
Ellen W Seely;Cynthia Maxwell - 通讯作者:
Cynthia Maxwell
Edinburgh Research Explorer Guidelines for the Development of Comprehensive Care Centers for Congenital Adrenal Hyperplasia: Guidance from the CARES Foundation Initiative
爱丁堡研究探索者先天性肾上腺增生综合护理中心发展指南:CARES 基金会倡议的指导
- DOI:
- 发表时间:
2018 - 期刊:
- 影响因子:0
- 作者:
R. Auchus;Selma FeldmanWitchel;Kelly R. Leight;Javier Aisenberg;Ricardo Azziz;T. Bachega;Linda A. Baker;Arlene B. Baratz;Laurence S. Baskin;Sheri A. Berenbaum;D. T. Breault;B. Cerame;Gerard S. Conway;Erica A. Eugster;Stephanie Fracassa;J. P. Gearhart;Mitchell E. Geffner;K. Harris;Richard S. Hurwitz;A. Katz;Brinda N. Kalro;Peter A. Lee;Gretchen Alger Lin;Karen J. Loechner;IanMarshall;Deborah P. Merke;C. Migeon;Walter L. Miller;Tamara L. Nenadovich;Sharon E. Oberfield;K. Pass;D. Poppas;Michele A. Lloyd;C. Quigley;F. Riepe;Richard C. Rink;S. Rivkees;David E Sandberg;Traci L. Schaeffer;R. Schlussel;Francis X. Schneck;Ellen W Seely;Diane Snyder;Phyllis W. Speiser;B. Therrell;C. VanRyzin;M. Vogiatzi;Michael P. Wajnrajch;Perrin C. White;Alan E. Zuckerman - 通讯作者:
Alan E. Zuckerman
Ellen W Seely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('Ellen W Seely', 18)}}的其他基金
Unique cardiovascular Risk Factors in Women Research and Mentoring Progam
女性研究和指导计划中独特的心血管危险因素
- 批准号:
8265868 - 财政年份:2010
- 资助金额:
$ 62.95万 - 项目类别:
Unique cardiovascular Risk Factors in Women Research and Mentoring Progam
女性研究和指导计划中独特的心血管危险因素
- 批准号:
7787959 - 财政年份:2010
- 资助金额:
$ 62.95万 - 项目类别:
Unique cardiovascular Risk Factors in Women Research and Mentoring Progam
女性研究和指导计划中独特的心血管危险因素
- 批准号:
8033082 - 财政年份:2010
- 资助金额:
$ 62.95万 - 项目类别:
Unique cardiovascular Risk Factors in Women Research and Mentoring Progam
女性研究和指导计划中独特的心血管危险因素
- 批准号:
8610940 - 财政年份:2010
- 资助金额:
$ 62.95万 - 项目类别:
Unique cardiovascular Risk Factors in Women Research and Mentoring Progam
女性研究和指导计划中独特的心血管危险因素
- 批准号:
8427358 - 财政年份:2010
- 资助金额:
$ 62.95万 - 项目类别:
FEMALE GENDER AND ITS INFLUENCE ON GENETIC EXPRESSION OF RISK GENES
女性性别及其对风险基因基因表达的影响
- 批准号:
7379265 - 财政年份:2006
- 资助金额:
$ 62.95万 - 项目类别:
DIETARY SALT INTAKE AND VASCULAR FUNCTION IN HEALTHY MEN
健康男性的膳食盐摄入量和血管功能
- 批准号:
7379284 - 财政年份:2006
- 资助金额:
$ 62.95万 - 项目类别:
Female gender & expression of risk genes in hypertension
性别 女性
- 批准号:
7010658 - 财政年份:2005
- 资助金额:
$ 62.95万 - 项目类别:
FEMALE GENDER AND ITS INFLUENCE ON GENETIC EXPRESSION OF RISK GENES
女性性别及其对风险基因基因表达的影响
- 批准号:
7204547 - 财政年份:2005
- 资助金额:
$ 62.95万 - 项目类别:
Blood Pressure in Postmenopausal Women: A GCRC Study
绝经后妇女的血压:GCRC 研究
- 批准号:
6889612 - 财政年份:2003
- 资助金额:
$ 62.95万 - 项目类别:
相似国自然基金
SK钾离子通道调控醛固酮分泌的分子机制及其对血压的影响
- 批准号:31771282
- 批准年份:2017
- 资助金额:60.0 万元
- 项目类别:面上项目
KCNJ5基因突变导致肾上腺醛固酮腺瘤发生的分子机制
- 批准号:81602477
- 批准年份:2016
- 资助金额:19.0 万元
- 项目类别:青年科学基金项目
新疆地区原发性醛固酮增多症不同亚型与KCNJ5基因及其相关类固醇关系的研究
- 批准号:81660139
- 批准年份:2016
- 资助金额:35.0 万元
- 项目类别:地区科学基金项目
基于醛固酮活化/SGK-1/ NF-kB通路诱导细胞增殖探讨"浊毒致瘀"的机制及化瘀解毒中药的调控作用
- 批准号:81473652
- 批准年份:2014
- 资助金额:74.0 万元
- 项目类别:面上项目
肾上腺皮质球状带细胞膜电位振荡的分子机制及其对醛固酮分泌的调节
- 批准号:31271240
- 批准年份:2012
- 资助金额:80.0 万元
- 项目类别:面上项目
相似海外基金
Origins of sex differences in the mechanisms of obesity-associated hypertension
肥胖相关高血压机制中性别差异的起源
- 批准号:
10678441 - 财政年份:2023
- 资助金额:
$ 62.95万 - 项目类别:
Sex and stress hormones control adrenal gland macrophage development and function"
性激素和应激激素控制肾上腺巨噬细胞的发育和功能"
- 批准号:
10629376 - 财政年份:2022
- 资助金额:
$ 62.95万 - 项目类别:
Identification of epigenetic targets in alcohol adrenal allostasis
酒精肾上腺动态平衡表观遗传靶点的鉴定
- 批准号:
10214954 - 财政年份:2021
- 资助金额:
$ 62.95万 - 项目类别:
Regulation of adrenal development and function by the mother's skeleton
母亲骨骼对肾上腺发育和功能的调节
- 批准号:
10671698 - 财政年份:2021
- 资助金额:
$ 62.95万 - 项目类别:
Regulation of adrenal development and function by the mother's skeleton
母亲骨骼对肾上腺发育和功能的调节
- 批准号:
10493319 - 财政年份:2021
- 资助金额:
$ 62.95万 - 项目类别: