Generation of Endothelial Cell Memory in Inflammatory Vascular Disease

炎症性血管疾病中内皮细胞记忆的产生

基本信息

批准号：
10671561
负责人：
Suellen D'Arc dos Santos Oliveira
金额：
$ 16.2万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-27 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10671561
关键词：
Abnormal Endothelial Cell Acute Address Animal Model Anti-Inflammatory Agents Antigens Apoptosis Apoptotic Area Blood Vessels Brazil Caveolins Cell Death Cell Death Induction Cell Survival Cell secretion Cells Cessation of life Characteristics Chicago Chronic Chronic Lung Injury Collaborations Communities Creativeness Cultural Backgrounds Curiosities Cytometry Cytoprotection Data Dedications Development Development Plans Disease Doctor of Philosophy Endothelial Cells Endothelium Environment Evaluation Faculty Fibrosis Functional disorder Generations Goals Growth Human Illinois Immune Immunity Immunobiology Impairment In Vitro Induction of Apoptosis Infection Inflammation Inflammatory Injury Institution Knowledge Leadership Learning Lesion Life Lung Lymphocyte Mediating Memory Mentors Methodology Modeling Molecular Target Mus Parasites Parasitic infection Persons Pharmacology Phase Phenotype Phosphorylation Process Proliferating Pulmonary Fibrosis Pulmonary Heart Disease Pulmonary Inflammation Pulmonary vessels Reporting Research Research Personnel Research Project Summaries Research Subjects Resistance Scaffolding Protein Schistosoma mansoni Schistosoma mansonii infection Signal Transduction Smooth Muscle Myocytes Students Technical Expertise Testing Th2 Cells Therapeutic Embolization Tissues Training Transforming Growth Factor beta Universities Vascular Diseases Vascular Proliferation Vascular remodeling Vesicle Voice Woman career career development caveolin 1 chemokine clinical development cytokine distinguished professor egg experience hypertension treatment imprint in vivo inhibitor inhibitor of apoptosis protein 2 injured insight inter-institutional lectures lung pressure molecular modeling novel overexpression pathogen pharmacologic pre-clinical prevent pulmonary arterial hypertension receptor recruit response skills success superresolution microscopy targeted treatment

项目摘要

Summary of the Research Project: Pulmonary arterial hypertension (PAH) is a life-threatening disease with no cure characterized by severe lesions in the pulmonary vessels due to hyperproliferation of vascular cells, including endothelial cells. The primary cause of these lesions is largely unknown, but several studies indicate they result from chronic inflammation, such as that caused by Schistosoma mansoni infection. ~10 million people infected with S. mansoni develop PAH (Sch-PAH). Thus, a better understanding of how the infection promotes the formation of vascular lesions will provide insights for identifying novel molecular targets for PAH treatment. Recently, we reported that endothelial cells that survive to chronic lung injury, show reduced expression of the anti-proliferative scaffolding protein caveolin-1 (Cav-1) and elevated response to pro-fibrotic TGF-β signaling. Activation of TGF-β requires recruitment of Th2 cells into the lungs, which in turn expands Cav-1 depleted endothelial cells and promote PAH. Although it is unknown how Cav-1-depleted endothelial cells contribute to Sch-PAH, our preliminary data indicate enhanced expression of inhibitor of apoptosis protein 2 (c-IAP2) may participate in this process. In line with this observation, data suggest that S. mansoni-primed endothelial cells retain in vitro a memory of the in vivo infection. Specifically, this memory is characterized by impaired function of the death associated receptor P2X7, which is controlled by Cav-1 expression. Thus, I hypothesize that while S. mansoni infection leads to lung endothelial cell death and secretion of c-IAP2, recipient cells generate a long- lasting survival memory required for endothelial-immune cell crosstalk and the development of Sch-PAH. Candidate & Institutional Environment: Dr. Oliveira is Junior Faculty at the University of Illinois at Chicago (UIC). She earned her Ph.D. in Immunobiology and M.Sc. in Pharmacology from the Federal University of Rio de Janeiro, Brazil. As a Latin woman, she grew up surrounded by different cultural backgrounds, and thus, learned how diversity is a crucial part of the human experience and existence itself. Dr. Oliveira’s career development plan combines the knowledge and technical expertise from her graduate and post-graduate training with novel methodologies and research subjects to build up a unique trajectory toward becoming a fully independent investigator. Specifically, Dr. Oliveira proposes advancing her leadership skills, strengthening her inter-institutional network, providing and organizing lectures inside and outside of her institution, and further engaging in mentoring and student evaluation. To achieve these goals, Dr. Oliveira built a team with distinguished Professors from the areas of expertise needed for both the scientific and professional success of her career development plan. In terms of the environment, Dr. Oliveira is located in an acclaimed research institution dedicated to discovering and distributing knowledge. Thus, along with her professional growth, Dr. Oliveira plans to promote the growth of the academic community as a whole by engaging all voices into an inclusive and creative environment required for continuous scientific progress and institutional excellence.

研究项目摘要：肺动脉高压（PAH）是一种危及生命的疾病，无法治愈其特征是由于血管细胞过度增殖而导致肺血管严重病变，这些病变的主要原因尚不清楚，但一些研究表明。它们是由慢性炎症引起的，例如约 1000 万人感染曼氏血吸虫引起的炎症。曼氏沙门氏菌感染后会发展为多环芳烃 (Sch-PAH)，因此可以更好地了解感染如何促进。血管病变的形成将为确定多环芳烃治疗的新分子靶点提供见解。最近，我们报道了慢性肺损伤后存活的内皮细胞显示出抗增殖支架蛋白 Caveolin-1 (Cav-1) 和对促纤维化 TGF-β 信号传导的升高反应。 TGF-β 的激活需要将 Th2 细胞募集到肺部，从而扩大 Cav-1 耗尽的细胞尽管尚不清楚 Cav-1 耗尽的内皮细胞如何促进 PAH。 Sch-PAH，我们的初步数据表明凋亡蛋白抑制剂 2 (c-IAP2) 的表达增强可能与这一观察结果一致，数据表明曼氏酵母引发的内皮细胞。具体来说，这种记忆的特点是功能受损死亡相关受体 P2X7，由 Cav-1 表达控制。曼氏沙门氏菌感染导致肺内皮细胞死亡并分泌c-IAP2，受体细胞产生长- 内皮-免疫细胞串扰和 Sch-PAH 发展所需的持久生存记忆。候选人和机构环境：奥利维拉博士是伊利诺伊大学芝加哥分校的初级教师她在里约联邦大学获得了免疫生物学博士学位和药理学硕士学位。作为一名拉丁女性，她在不同的文化背景中长大，因此，了解多样性如何成为人类经验和存在本身的重要组成部分。发展计划结合了她的研究生和研究生培训的知识和技术专长凭借新颖的方法论和研究主题，建立一条独特的轨迹，成为一个全面的具体来说，奥利维拉博士建议提高她的领导技能，加强她的能力。机构间网络，在机构内外提供和组织讲座，并进一步为了实现这些目标，奥利维拉博士建立了一个团队，致力于指导和学生评估。来自科学和专业成功所需的专业领域的杰出教授在她的职业发展计划环境方面，奥利维拉博士位于一个备受赞誉的研究室。因此，随着她的专业成长，博士。奥利维拉计划通过让所有声音参与进来，促进整个学术界的发展。科学不断进步和机构卓越所需的包容性和创造性环境。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cardiopulmonary Pathogenic Networks: Unveiling the Gut-Lung Microbiome Axis in Pulmonary Arterial Hypertension.

心肺致病网络：揭示肺动脉高压中的肠肺微生物组轴。

DOI：
发表时间：
2023-03-15
期刊：
影响因子：
24.7
作者：
Oliveira; Suellen Darc
通讯作者：
Suellen Darc

Thiostrepton-Nanomedicine, a TLR9 Inhibitor, Attenuates Sepsis-Induced Inflammation in Mice.

Thiostrepton-Nanomedicine 是一种 TLR9 抑制剂，可减轻小鼠脓毒症引起的炎症。

DOI：
发表时间：
2023
期刊：
影响因子：
4.6
作者：
Esparza, K;Oliveira, S D;Castellon, M;Minshall, R D;Onyuksel, H
通讯作者：
Onyuksel, H

Schistosomiasis-associated pulmonary hypertension unveils disrupted murine gut-lung microbiome and reduced endoprotective Caveolin-1/BMPR2 expression.

血吸虫病相关的肺动脉高压揭示了小鼠肠肺微生物组的破坏和内保护性 Caveolin-1/BMPR2 表达的减少。

DOI：
发表时间：
2023
期刊：
影响因子：
0
作者：
Marinho, Ygor;Villarreal, Elizabeth S;Aboagye, Sammy Y;Williams, David L;Sun, Jun;Silva, Claudia L M;Lutz, Sarah E;Oliveira, Suellen D
通讯作者：
Oliveira, Suellen D

Insights on the Gut-Mesentery-Lung Axis in Pulmonary Arterial Hypertension: A Poorly Investigated Crossroad.

肺动脉高压中肠道-肠系膜-肺轴的见解：一个研究不足的十字路口。

DOI：
发表时间：
2022-05
期刊：
影响因子：
0
作者：
Oliveira; Suellen Darc
通讯作者：
Suellen Darc

Hypoxia-induced pulmonary hypertension upregulates eNOS and TGF-β contributing to sex-linked differences in BMPR2 +/R899X mutant mice.

缺氧诱导的肺动脉高压上调 eNOS 和 TGF-β，导致 BMPR2 /R899X 突变小鼠的性别差异。

DOI：
发表时间：
2022-10
期刊：
影响因子：
2.6
作者：
Erewele, Ejehi O;Castellon, Maricela;Loya, Omar;Marshboom, Glenn;Schwartz, Andrew;Yerlioglu, Kayla;Callahan, Christopher;Chen, Jiwang;Minshall, Richard D;Oliveira, Suellen D
通讯作者：
Oliveira, Suellen D