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.

抽象的 塞缪尔·蒙塔尔沃（Samuel Montalvo）博士是来自西班牙裔（墨西哥）遗产的美国公民。最初来自德克萨斯州埃尔帕索（El Paso）博士 蒙塔尔沃（Montalvo）从德克萨斯大学埃尔帕索（El Paso）和 他是该研究补充剂促进多样​​性应用的绝佳候选人。蒙塔尔沃博士将工作 根据父母的赠款，标题为“颈动脉的合成3D模型，用于研究运动引起的变化 在内皮基因表达中”（SC2GM140952）授予Alvaro Gurovich博士，主要目的是 使用3D生物印刷技术开发人类颈动脉的3D合成模型来模拟 体内个性化轴诱导的血流模式和内皮剪切应力，并确定 体外内皮培养细胞的基因表达/转录和分子变化。蒙塔尔沃博士 将在3项研究中起作用，其中2个与父母赠款的特定目的相关，以假设3D 颈动脉的合成模型将响应运动引起的血液流动模式作为正常的颈动脉 动脉（特定目标1）和在相似的血流模式下的内皮培养细胞和剪切应力将 增加动脉粥样硬化保护mRNA/蛋白质（例如eNOS，PGI2和SOD）和 结构mRNA/蛋白质（例如肌动蛋白，硫酸肝素蛋白聚糖[糖蛋白糖]和α-肌动蛋白捆扎应激 纤维），以及促骨硬化和促炎的mRNA/蛋白质表达的减少（例如，ICAM-1， VCAM-1和ET-1）以相似的强度依赖性方式（特定目标2）。第三项研究是一项平行研究 回应父母赠款审稿人的一些评论。目的是确定 传统的2D剪切应力模型与新颖的3D合成模型之间的差异 父母赠款。为了实现这一目的，蒙塔尔沃博士将使用收集的数据来开发飞行员3D 模型并比较了2D和3D模型中剪切应力下内皮细胞中蛋白质/基因的表达。 他假设3D模型将能够增加内皮细胞蛋白含量，因为3D更多 如在高强度运动中所观察到的那样，生理性忍受了更高的剪切应力。此外 提出的研究项目，蒙塔尔沃博士将制定一项强大的精神计划计划 不同的职业阶段（即讲师，助理，副教育和完整教授）。父母赠款，具体 研究项目以及Mentalship计划和团队将增强Montalvo博士的研究能力和 增加了他在研究机构中获得任期教师职位的机会。