The Microvascular Aging and Eicosanoids - Women's Evaluation of Systemic Aging Tenacity (MAE-WEST) ("You are never too old to become younger!") Specialized Center for Research Excellence (SCORE)

微血管老化和类二十烷酸 - 女性全身老化韧性评估 (MAE-WEST)（“你永远不会太老，变得更年轻！”）卓越研究专业中心 (SCORE)

基本信息

批准号：
10817498
负责人：
Cathleen Noel Bairey Merz
金额：
$ 16.47万
依托单位：
CEDARS-SINAI MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-06-30
项目状态：
未结题

项目摘要

Project Abstract – MAE-WEST SCORE Overall Women age differently than men across the lifespan, culminating in a female predominance in morbid chronic diseases such as heart failure with preserved ejection fraction, Alzheimer’s disease and related dementias, and chronic kidney disease. Women also tend to develop multi-organ syndromes (heart-brain, heart-kidney) more frequently than men. The mechanisms underlying sex-specific differences in multi-organ dysfunction remain poorly understood. Prior work indicates that women exhibit accelerated microvascular aging, a process implicated in disorders of the heart, brain, and kidney. In this context, systemic inflammation has emerged as a primary driver of both microvascular dysfunction and the development of these chronic disease states. Preliminary data from our group indicates that eicosanoids, a diverse group of bioactive lipids that serve as the upstream mediators of systemic inflammation, can influence endothelial cell function, exhibit sexual dimorphism in circulating plasma, and are related to certain vascular phenotypes. Given these findings, we hypothesize that sexual dimorphism in both local and systemic eicosanoid variation contributes to sex differences in microvascular dysfunction and, in turn, to sex differences in age-related multi-organ disease. Motivated by our early findings and the critical need to understand the determinants and drivers of sex differences in age-related disease outcomes, we propose to create the Microvascular Aging and Eicosanoids –Women’s Evaluation of Systemic aging Tenacity (MAE-WEST) Specialized Center of Research Excellence (SCORE) on Sex Differences. Leveraging our collective expertise, we plan to advance the understanding of sex-specific molecular drivers of chronic microvascular and end-organ disease through 3 foundational projects. In Project 1, we will examine longitudinal variation in circulating eicosanoid levels in relation to age-related alterations in microvascular function in end-organ (cardiovascular, neurocognitive, renal) disease traits in 2 large community cohorts. In Project 2, we will prospectively enroll and deeply phenotype a cohort of women and men to assess the relation of eicosanoids with organ-specific as well as global burden of microvascular disease, as well as their response to a trial of intensive medical therapy with FDA-approved agents (statins and ACEi/ARB). Finally, in Project 3, we will study the mechanistic role of sex-specific eicosanoid signaling on human endothelial cell function and on microvascular function in experimental models of organ-specific disease as well as whole organism aging. As an integral part of this SCORE, we will establish a Career Enhancement Center that will provide robust training and mentorship for trainees and junior investigators. Collectively, this highly collaborative and innovative SCORE aims to transform our understanding of sex differences in microvascular and chronic multi-organ diseases and, in turn, enable effective interventions through inter-disciplinary science, education, and advocacy. !

项目摘要 – MAE-WEST 总体评分在整个生命周期中，女性的年龄与男性不同，最终导致女性在慢性病中占主导地位射血分数保留的心力衰竭、阿尔茨海默病和相关痴呆等疾病，以及女性也更容易患上多器官综合征（心脑、心肾）。多器官功能障碍中性别特异性差异的机制仍然存在。此前的研究表明，女性表现出加速的微血管老化这一过程。在这种情况下，全身性炎症已成为一种与心脏、大脑和肾脏疾病有关的疾病。微血管功能障碍和这些慢性疾病状态发展的主要驱动因素。我们小组的初步数据表明，类二十烷酸是一组多样化的生物活性脂质，可作为全身炎症的上游介质，可以影响内皮细胞功能，表现出性别二态性存在于循环血浆中，并且与某些血管表型相关。鉴于这些发现，我们发现了这一点。局部和全身类二十烷酸变异的性别二态性导致微血管的性别差异功能障碍，进而导致与年龄相关的多器官疾病的性别差异。以及了解年龄相关疾病性别差异的决定因素和驱动因素的迫切需要结果，我们建议创建微血管老化和类二十烷酸 – 女性全身评估老化韧性 (MAE-WEST) 性别差异专业卓越研究中心 (SCORE)。利用我们的集体专业知识，我们计划增进对性别特异性分子驱动因素的理解在项目 1 中，我们将通过 3 个基础项目研究慢性微血管和终末器官疾病。循环类二十烷酸水平的纵向变化与年龄相关的微血管变化有关两个大型社区队列中终末器官（心血管、神经认知、肾脏）疾病特征的功能。项目 2，我们将前瞻性地招募一组女性和男性并对其进行深入表型分析，以评估这种关系类二十烷酸对器官特异性和整体微血管疾病负担的影响及其反应使用 FDA 批准的药物（他汀类药物和 ACEi/ARB）进行强化药物治疗的试验最后，在项目 3 中，我们将研究性别特异性类二十烷酸信号传导对人内皮细胞功能的机制作用以及器官特异性疾病以及整个有机体衰老实验模型中的微血管功能。作为该 SCORE 的组成部分，我们将建立一个职业提升中心，提供强有力的培训总的来说，这个高度协作和创新的 SCORE。旨在改变我们对微血管和慢性多器官疾病性别差异的理解，反过来，通过跨学科的科学、教育和宣传来实现有效的干预。！

项目成果

期刊论文数量（37）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Syndrome of Nonobstructive Coronary Artery Diseases: A Comprehensive Overview of Open Artery Ischemia.

非阻塞性冠状动脉疾病综合征：开放性动脉缺血的综合概述。

DOI：
发表时间：
2021
期刊：
影响因子：
0
作者：
Ya'qoub, Lina;Elgendy, Islam Y;Pepine, Carl J
通讯作者：
Pepine, Carl J

INOCA and MINOCA: Are Women's Heart Centres the Answer to Understanding and Management of These Increasing Populations of Women (and Men)?

INOCA 和 MINOCA：女性心脏中心是理解和管理这些不断增加的女性（和男性）人口的答案吗？

DOI：
发表时间：
2022-10
期刊：
影响因子：
0
作者：
Pacheco, Christine;Luu, Judy;Mehta, Puja K;Wei, Janet;Gulati, Martha;Bairey Merz, C Noel
通讯作者：
Bairey Merz, C Noel

Influence of the COVID-19 Pandemic on Author Sex and Manuscript Acceptance Rates among Pulmonary and Critical Care Journals.

COVID-19 大流行对肺部和重症监护期刊作者性别和稿件接受率的影响。

DOI：
发表时间：
2023-02
期刊：
影响因子：
8.3
作者：
Gershengorn, Hayley B;Vranas, Kelly C;Ouyang, David;Cheng, Susan;Rogers, Angela J;Schweiger, Liana;Cooke, Colin R;Slatore, Christopher G
通讯作者：
Slatore, Christopher G

Ischemia and no obstructive coronary arteries (INOCA): A narrative review.

缺血且无阻塞性冠状动脉（INOCA）：叙述性回顾。

DOI：
发表时间：
2022-12
期刊：
影响因子：
5.3
作者：
Mehta, Puja K;Huang, Jingwen;Levit, Rebecca D;Malas, Waddah;Waheed, Nida;Bairey Merz, C Noel
通讯作者：
Bairey Merz, C Noel

Bending Primordial Trajectories Away From Heart Failure.

弯曲原始轨迹，远离心力衰竭。