Synthetic 3D Model of the Carotid Artery to Study Exercise-Induced Changes in Endothelial Gene Expression

用于研究运动引起的内皮基因表达变化的颈动脉合成 3D 模型

基本信息

批准号：
10606026
负责人：
Alvaro N Gurovich
金额：
$ 8.3万
依托单位：
UNIVERSITY OF TEXAS EL PASO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-17 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10606026
关键词：
3-Dimensional Actins Atherosclerosis Award Blood flow Cardiovascular system Carotid Arteries Clinical Cultured Cells Data Doctor of Philosophy Endothelial Cells Endothelin-1 Endothelium Epigenetic Process Epoprostenol Exercise Faculty Gene Expression Gene Proteins Genetic Transcription Glycocalyx Health Professional Hispanic Human In Vitro Inflammatory Institution Intercellular adhesion molecule 1 Medicine Mentors Mentorship Messenger RNA Mexican Modeling Molecular Nurses Pattern Physiological Positioning Attribute Proteins Published Comment Rehabilitation therapy Research Research Project Grants Stress Fibers Technology Texas Universities Vascular Cell Adhesion Molecule-1 Work alpha Actinin bioprinting career exercise intensity exercise physiologist heparin proteoglycan improved in vivo lecturer mid-career faculty novel parent grant physical therapist programs protein expression senior faculty shear stress stroke survivor tenure track three-dimensional modeling

项目摘要

Abstract Dr. Samuel Montalvo is a US citizen from Hispanic (Mexican) heritage. Originally from El Paso, Texas, Dr. Montalvo has earned his Bachelors, Masters, and PhD degrees from The University of Texas at El Paso and he is a great candidate for this Research Supplements to Promote Diversity application. Dr. Montalvo will work under the parent grant entitled “Synthetic 3D Model of the Carotid Artery to Study Exercise-Induced Changes in Endothelial Gene Expression” (SC2GM140952) awarded to Dr. Alvaro Gurovich, which main purpose is to develop a 3D synthetic model of the human carotid artery using 3D bio-printing technology to simulate in vivo personalized AX-induced blood flow patterns and endothelial shear stress and to determine gene expression/transcription and molecular changes in endothelial cultured cells in vitro. Dr. Montalvo will work in 3 studies, 2 of them associated with the parent grant specific aims that hypothesize that a 3D synthetic model of the carotid artery will respond to exercise-induced blood flow patterns as a normal carotid artery (Specific Aim 1) and that endothelial cultured cells under similar blood flow patterns and shear stress will increase the expression of atherosclerosis-protective mRNA/proteins (e.g., eNOS, PGI2, and SOD) and structural mRNA/proteins (e.g., actin, heparin sulfate proteoglycan [glycocalyx], and α-actinin-bundled stress fibers), and a decrease of pro-atherosclerosis and pro-inflammatory mRNA/protein expression (e.g., ICAM-1, VCAM-1, and ET-1) in a similar intensity-dependent manner (Specific Aim 2). The third study is a parallel study responding to some of the comments from the reviewers of the parent grant. The purpose is to determine the differences between the traditional 2D shear stress model and the novel 3D synthetic model proposed in the parent grant. To accomplish this purpose, Dr. Montalvo will work with collected data to develop the pilot 3D model and compared protein/gene expression in endothelial cells under shear stress in the 2D and 3D models. He hypothesizes that the 3D model will be able to increase endothelial cell protein content as the 3D is more physiological to endure higher shear stress as the ones observed during high intensity exercise. In addition, to the research projects proposed, Dr. Montalvo will have a strong mentorship plan including 4 mentors in different career stages (i.e., lecturer, Assistant, Associate, and Full Professors). The parent grant, the specific research projects, and the mentorship plan and team will enhance Dr. Montalvo’s research capacity and increase his chances to obtain a tenure track faculty position in a research institution.

抽象的塞缪尔·蒙塔尔沃博士是一位拥有西班牙裔（墨西哥）血统的美国公民，来自德克萨斯州埃尔帕索。蒙塔尔沃在德克萨斯大学埃尔帕索分校获得了学士、硕士和博士学位，他是蒙塔尔沃博士将工作的研究补充促进多样性申请的绝佳候选人。根据题为“用于研究运动引起的变化的颈动脉合成 3D 模型”的家长资助内皮基因表达” (SC2GM140952) 授予 Alvaro Gurovich 博士，其主要目的是利用3D生物打印技术开发人体颈动脉3D合成模型来模拟体内个性化 AX 诱导的血流模式和内皮剪切应力，并确定 Montalvo 博士在体外培养的内皮细胞中的基因表达/转录和分子变化。将参与 3 项研究，其中 2 项与家长资助的特定目标相关，这些目标旨在实现 3D 颈动脉的合成模型将像正常颈动脉一样对运动引起的血流模式做出反应动脉（具体目标 1）和内皮培养细胞在相似的血流模式和剪切应力下将增加动脉粥样硬化保护性 mRNA/蛋白（例如 eNOS、PGI2 和 SOD）的表达结构 mRNA/蛋白质（例如肌动蛋白、硫酸肝素蛋白聚糖 [糖萼] 和 α-肌动蛋白捆绑应激纤维），以及促动脉粥样硬化和促炎 mRNA/蛋白表达（例如 ICAM-1、 VCAM-1 和 ET-1）以类似的强度依赖性方式（具体目标 2）。回应母基金评审员的一些意见，目的是确定传统的 2D 剪应力模型和新颖的 3D 合成模型之间的差异为了实现这一目的，Montalvo 博士将利用收集到的数据来开发 3D 试点项目。模型并比较 2D 和 3D 模型中剪切应力下内皮细胞的蛋白质/基因表达。他认为 3D 模型将能够增加内皮细胞蛋白质含量，因为 3D 模型更加逼真。生理上承受高强度运动期间观察到的更高的剪切应力。对于拟议的研究项目，Montalvo 博士将制定一个强有力的指导计划，其中包括 4 名导师不同的职业阶段（即讲师、助理、副教授和正教授）。研究项目、导师计划和团队将增强蒙塔尔沃博士的研究能力和增加他在研究机构获得终身教职的机会。