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

• 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
• 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

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.

摘要 博士塞缪尔蒙塔尔沃是一个美国公民从西班牙裔（墨西哥）遗产。来自德克萨斯州的埃尔帕索，博士。 蒙塔尔沃拥有德克萨斯大学埃尔帕索分校的学士、硕士和博士学位， 他是这个研究补充，以促进多样性应用的伟大候选人。蒙塔尔沃医生可以 在题为“研究脑卒中引起的变化的颈动脉合成3D模型”的家长资助下， 在内皮基因表达”（SC2 GM 140952）授予博士阿尔瓦罗Gurovich，其主要目的是 使用3D生物打印技术开发人体颈动脉的3D合成模型，以模拟 体内个性化AX诱导的血流模式和内皮剪切应力，并确定 体外培养内皮细胞的基因表达/转录和分子变化。蒙塔尔沃医生 我将在3项研究中工作，其中2项与父母补助金的具体目标有关，假设3D 颈动脉的合成模型将像正常颈动脉一样对运动诱导的血流模式作出反应 动脉（具体目标1），内皮细胞培养细胞在类似的血流模式和剪切应力下， 增加动脉粥样硬化保护性mRNA/蛋白的表达（例如，eNOS、PGI 2和SOD）和 结构mRNA/蛋白质（例如，肌动蛋白、硫酸肝素蛋白聚糖[糖萼]和α-肌动蛋白束应激 纤维），以及促动脉粥样硬化和促炎mRNA/蛋白表达的降低（例如，ICAM-1， VCAM-1和ET-1）以类似的强度依赖性方式（特异性目的2）。第三项研究是平行研究 回应来自母基金评审员的一些评论。目的是确定 传统的2D剪应力模型和新的3D合成模型之间的差异， 家长补助为了实现这一目的，蒙塔尔沃博士将利用收集到的数据开发试验性3D 模型，并比较了2D和3D模型中剪切应力下内皮细胞中的蛋白质/基因表达。 他假设3D模型将能够增加内皮细胞蛋白质含量，因为3D模型更加复杂。 生理上耐受更高的剪切应力，如在高强度运动期间观察到的。此外，要 蒙塔尔沃博士将有一个强大的导师计划，包括4名导师， 不同的职业阶段（即，讲师，助理，副教授和全职教授）。父母补助金， 研究项目，导师计划和团队将提高蒙塔尔沃博士的研究能力， 增加他在研究机构获得终身教职的机会。