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Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women

年轻女性的动脉粥样硬化、免疫介导的炎症和低雌激素血症

基本信息

批准号：
10022160
负责人：
Chrisandra Lee Shufelt
金额：
$ 19.8万
依托单位：
CEDARS-SINAI MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10022160
关键词：
Academy Address Advocate Age Amenorrhea American Anti-Inflammatory Agents Atherosclerosis Biology Biometry Birth Blood Vessels Cardiovascular Diseases Cause of Death Cessation of life Clinical Investigator Clinical Research Clinical Trials Design Coronary Arteriosclerosis Data Death Rate Development Plans Discipline of obstetrics Dose Endothelium Estradiol Estrogens Etiology Event Future Goals Gynecology Hormonal Hypothalamic structure Immune Immune response Immunology Inflammation Inflammatory Investigation Ischemia Link Literature Measures Medial Mediating Menopause Menstrual cycle Mentors Modality Mutation Natural Immunity Osteoporosis Pathway interactions Patients Pediatrics Peripheral Phenotype Placebos Play Polycystic Ovary Syndrome Premenopause Progesterone Randomized Research Research Project Grants Risk Risk Factors Role Route Signs and Symptoms T-Lymphocyte Testing Thick Tissues Training Translating Turner&apos s Syndrome Woman Women&apos s Health Work adaptive immunity age group arterial tonometry cardiovascular disorder risk career career development clinical care college cytokine design double-blind placebo controlled trial early onset experience functional hypothalamic amenorrhea hormone therapy immunoregulation improved multidisciplinary novel novel strategies older men older women patient oriented research pre-clinical premature prevent public health relevance research and development response skills young man young woman

项目摘要

DESCRIPTION (provided by applicant): Premature cardiovascular disease (CVD) is the leading cause of death in young women. While death rates from CVD have declined in all other age groups, they are continuing to increase in women between the ages of 35 and 44 years and traditional CVD risk factors are not capturing this risk, leaving much unexplained. Prior research has demonstrated that irregular menstrual cycling in young women poses up to a 50% increased CVD risk. Women with Turner's syndrome, a genetic defect resulting in prolonged hypoestrogenemia (HypoE) from birth, have premature deaths due to accelerated CVD. Additionally, HypoE of hypothalamic origin has been associated with premenopausal obstructive coronary artery disease in women with signs and symptoms of ischemia. Taken together these data indicate that HypoE in premenopausal women is associated with accelerated CVD; and the mechanism(s) for these associations are unknown. It is established that immune- mediated inflammation plays a role in atherosclerosis, and estrogen has immunomodulatory effects resulting in suppression of pro-inflammatory cytokines while increasing anti-inflammatory cytokines. Furthermore, there is a large body of literature that demonstrates increased proinflammatory cytokines during estrogen loss after menopause. We hypothesize that HypoE in premenopausal women is associated with pre-clinical CVD, and that estrogen-mediated increases immune-mediated inflammation is a mechanistic pathway. We plan to: 1) investigate the relationship between HypoE, vascular function and preclinical CVD; 2) investigate the relationship between HypoE and immune-mediated inflammation; 3) evaluate in a randomized, double-blinded, placebo-controlled trial the impact of 4 weeks of transdermal estradiol followed by 2 weeks of estrogen plus progesterone in women with HypoE on vascular function and immune-mediated inflammation. Our study is important because it has the potential to identify a novel CVD risk factor in young women as well as an associated immune-mediated pathway. It is estimated that up to 34% of premenopausal women have secondary amenorrhea resulting in HypoE, that is 1.62 million US women between the ages of 18 and 44 years, making it more common etiology for menstrual cycle disruption than polycystic ovary syndrome. The American Academy of Pediatrics and the American College of Obstetrics and Gynecology have advocated that the menstrual cycle should be considered a "vital sign" due to the importance of estrogen on tissues throughout the body. For example, it has already well-established that HypoE in premenopausal women results in early-onset osteoporosis and that the immune response related to this osteoporosis is altered. This K23 application also addresses the important need to train qualified clinical investigators with the skills to work with experts related to vascular biology, atherosclerosis, immunology, and clinical trial design. The goal is to build on the applicant's experience in biostatistics, women's health and endogenous and exogenous estrogen by acquiring additional skills required for a successful independent clinical research career.

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

After menopause, is an enlarging middle, an enlarging cardiovascular risk factor?

绝经后，腰围增大是心血管疾病的危险因素吗？

DOI：
10.1097/gme.0000000000001620
发表时间：
2020
期刊：
Menopause (New York, N.Y.)
影响因子：
0
作者：
Lee,JulieJ;Shufelt,ChrisandraL
通讯作者：
Shufelt,ChrisandraL

Changes in Vascular Function from Preconception to Postpartum Among Mongolian Women.

蒙古女性从受孕前到产后血管功能的变化。

DOI：
10.1089/jwh.2021.0360
发表时间：
2022
期刊：
Journal of women's health (2002)
影响因子：
0
作者：
Enkhmaa,Davaasambuu;Ganmaa,Davaasambuu;Tanz,LaurenJ;Rich-Edwards,JanetW;Stuart,JenniferJ;Enkhtur,Shonkhuuz;Gantsetseg,Garmaa;Batkhishig,Bandi;Fitzmaurice,Garrett;Bayalag,Munkhuu;Nasantogtokh,Erdenebileg;BaireyMerz,CNoel;Shufel
通讯作者：
Shufel

A clinical prescription for heart health in midlife women.

中年女性心脏健康的临床处方。