Endothelial Cell Mechanical Dysfunction in Early Stage Atherosclerosis

动脉粥样硬化早期的内皮细胞机械功能障碍

• 批准号: 9332188
• 负责人: Robert Steward
• 金额: $ 14.74万
• 依托单位: UNIVERSITY OF CENTRAL FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9332188
• 关键词: Adherens Junction; Aerospace Engineering; Agonist; Arterial Fatty Streak; Atherosclerosis; Award; Biochemical; Biological Sciences; Biomedical Research; Blood Vessels; Book Chapters; Books; Cardiovascular Diseases; Cardiovascular Pathology; Cardiovascular system; Career Choice; Cell-Cell Adhesion; Cells; Cities; Data; Deposition; Endothelial Cells; Endothelium; Engineering; Ensure; Environment; Esters; Event; Florida; Foam Cells; Functional disorder; Funding; Future; Generations; Goals; Health Sciences; Immunology; In Vitro; Inflammation; Inflammatory; Injury; Intercellular Junctions; Interdisciplinary Study; International; Investigation; Knowledge; Lead; Leukocytes; Link; Lipids; Lipoproteins; Low-Density Lipoproteins; Mammalian Cell; Measures; Mechanics; Medical; Medical Research; Medical center; Medicine; Mentors; Methods; Molecular Biology; Morphology; Paper; Pathogenesis; Pediatric Hospitals; Penetration; Peripheral; Permeability; Pharmacology; Play; Prevention; Process; Protein Family; Proteins; Publications; Publishing; Recruitment Activity; Reporting; Research; Research Institute; Research Personnel; Resistance; Role; Scientist; Site; Tea; Testing; Text; Tight Junctions; Time; Training; Universities; Very low density lipoprotein; Veterans; authority; base; bench to bedside; career; cholesterol control; college; cytokine; design; experience; experimental study; fluid flow; insight; macrophage; mechanical drive; mechanical force; monolayer; novel; novel strategies; novel therapeutics; oxidation; oxidized low density lipoprotein; prevent; professor; programs; public health relevance; response; skills; success; technology development

 DESCRIPTION (provided by applicant): The PI is an assistant professor and the first dual hire between the Department of Mechanical and Aerospace Engineering and College of Medicine at the University of Central Florida. His background is in mechanical engineering and his research experiences have primarily focused on the development of technologies to mechanically stimulate mammalian cells and investigation of associated morphological responses. A total of thirteen publications have been produced thus far, including five first-author publications, two book chapters, and one equal contribution. The PI is highly motivated become an independent investigator in the cardiovascular field, but the PI's past research to date has only been peripherally related to the field. Furthermore, the PI believes the best treatment for many cardiovascular diseases is prevention at its earliest stages. Early stage atherosclerosis, for example, involves the entry and accumulation of low density lipoprotein (LDL) within the endothelium and leukocyte transmigration across the endothelium eventually yielding foam cells, the precursors of atherosclerotic plaques 1-9. Present during each of the previously mentioned processes within the endothelial monolayer are innate cell-cell adhesion forces10-15, whose roles and underlying biomolecular components have yet to be discovered. Therefore, the proposed award will investigate the hypothesis that decreased cell-cell junction activity decreases cell-cell adhesion forces, prompting increased LDL penetration and increased leukocyte transmigration across the endothelium under disturbed fluid flow. To test the above hypothesis a training plan is proposed that will allow the PI to develop expertise essential to the completion of this project in the following fields; molecular biology, atherosclerosis, and immunology. To ensure that the PI gains these skill sets the PI will be mentored by Dr. Sampath Parthasarathy. Dr. Parthasarathy is an internationally recognized authority on atherosclerosis. He has published over 150 papers on the topic (out of over 250) and has written a text book on "Modified Lipoproteins in the Pathogenesis of Atherosclerosis". His mentoring and guidance will therefore be invaluable to the success of the PI. Furthermore, the PI's training will take place in UCF's College of Medicine, which is located on Orlando's Medical City campus. This health and life sciences research park also includes the Sanford-Burnham Medical Research Institute, Nemour's Children Hospital, and Veterans Affairs Orlando Medical Center, providing an ideal biomedical research environment for the PI. Successful completion of this training award will put the PI on a career path to achieve the following goals; 1) to become an established investigator in the cardiovascular field and 2) obtain preliminary data to apply for future RO1 funding. In addition, the very long term career goal of the PI is to establish a multidisciplinary research tea that will consist of other independent investigators who are engineers, clinicians, and scientists to apply for PO1 funding and establish a research program in cardiovascular pathology aimed at developing novel bench-to-bedside cardiovascular therapies that would consist of treating cardiovascular disease at the cellular level.

 描述（由适用提供）：PI是助理教授，也是中央佛罗里达大学机械和航空航天工程系与医学院之间的第一个双重员工。他的背景是机械工程，他的研究经验主要集中于技术刺激哺乳动物细胞和研究相关形态反应的技术的发展。到目前为止，总共已经制作了13个出版物，其中包括五个第一专人出版物，两个书籍章节和一个同等的贡献。 PI是高度动机的，成为心血管领域的独立研究者，但是PI迄今为止的研究仅与该领域有关。此外，PI认为，许多心血管疾病的最佳治疗方法是最早的预防。例如，早期动脉粥样硬化涉及在山上跨森植物的山植物和白细胞转移中的低密度脂蛋白（LDL）的进入和积累最终产生泡沫细胞，这是动脉粥样硬化斑块的前体1-9。在单位层中前面提到的过程中，存在于先天细胞 - 细胞粘合力10-15，其作用和潜在的生物分子成分尚未发现。因此，拟议的奖励将调查一个假设，即降低细胞 - 细胞连接活性会降低细胞 - 细胞粘附力，促使LDL渗透增加并增加白细胞在受影响的液体流动下整个内皮的透射率。为了检验上述假设，提出了培训计划，该计划将使PI能够发展为 在以下字段中完成了该项目；分子生物学，动脉粥样硬化和免疫学。为了确保PI获得这些技能设定，PI将由Sampath Parthasarathy博士进行修复。 Parthasarathy博士是动脉粥样硬化的国际认可的权威。他已经发表了有关该主题的150篇论文（超过250个），并写了一本关于“动脉粥样硬化发病机理中修饰的脂蛋白”的教科书。因此，他的心理和指导对于PI的成功将是无价的。此外，PI的培训将在 UCF的医学院，位于奥兰多的医疗城校园。该健康与生命科学研究园还包括Sanford-Burnham医学研究所，Nemour的儿童医院和退伍军人事务中心，为PI提供了理想的生物医学研究环境。成功完成该培训奖将使PI踏上实现以下目标的职业道路； 1）成为心血管领域的既定研究者，2）获取初步数据以申请未来的RO1资金。此外，PI的长期职业目标是建立一种多学科研究茶，该茶将由其他独立研究人员组成，这些研究人员是工程师，临床医生和科学家，申请PO1资金并在心血管病理学领域建立研究计划，旨在开发新型的基准对伴式心血管疗法，这些疗法将包括治疗心脏病患者的蜂窝疾病。