The Role of MicroRNA 181b in the Development of Vascular Stiffness with Age

项目概要 候选人：Eric Tuday，医学博士、哲学博士，是助理教授，并在该部门获得双重任命 犹他大学心脏病学和弗吉尼亚州盐湖城转化生理学实验室。博士。 Tuday 的研究重点是 miR-181b 表达对年龄相关大细胞发育的影响 动脉僵硬。 Tuday 博士的长期目标是独立指导一个外部资助的实验室 研究重点是衰老的血管生物学和解决与年龄相关的血管疾病。 职业发展：该奖项将在 Tuday 博士现有的基础上支持他的职业发展 心血管生理学培训。具体来说，Tuday 博士将接受有关规划和实施的广泛培训。 执行评估啮齿动物整个血管和个体平滑肌健康的研究。职业生涯 发展计划概述了在以下领域培训候选人的协调努力：血管生物学 老化；评估与病理状态、动物遗传模型和状态相关的分子途径 最先进的细胞询问方法；旨在促进更好地理解的教学课程作业 治疗产品开发、动物研究和生物统计学的基础知识；并且，定期出席 在血管老化、遗传学和分子生物学会议上；最后是接触教学。 环境：犹他大学为Tuday博士的职业发展提供了理想的环境。这个 环境提供了完成本 K08 提案期间拟议研究所需的所有资源。 犹他大学还为职业发展的正式和非正式培训提供了丰富的环境。 研究：该研究项目的中心假设是 microRNA-181b 与年龄相关的减少 表达水平导致促炎症途径失调，最终导致炎症增加 大动脉僵硬。众所周知，microRNA-181b 对血管健康有益，并且水平 随着年龄的增长而减少；我们寻求了解这些机制。虽然 microRNA 的许多机制 181b 已被描述，我们认为存在受 microRNA-181b 影响的未经研究的途径 意义重大，因为它们与血管健康有关，特别是与血管平滑肌细胞（VSMC）有关。最后，我们 假设慢性、VSMC 特异性、microRNA-181b 过度表达可以预防与年龄相关的 增加大动脉僵硬度，最终保持心血管健康。

PROJECT SUMMARY Candidate: Eric Tuday, MD, PhD is an assistant professor with a dual appointment to the Division of Cardiology at the University of Utah and the Translational Physiology Laboratory at Salt Lake City VA. Dr. Tuday's research is focused on the impact of miR-181b expression on the development of age-related large artery stiffness. Dr. Tuday's long-term goal is to independently direct an extramurally funded laboratory with research focused on the vascular biology of aging and addressing age-related vascular diseases. Career Development: This award will support Dr. Tuday's career development by building on his existing training in cardiovascular physiology. Specifically, Dr. Tuday will receive extensive training in the planning and execution of studies assessing whole vessel and individual smooth muscle health in rodents. The career development plan outlines a coordinated effort to train the candidate in areas including: vascular biology of aging; assessment of molecular pathways pertinent to pathologic states, animal genetic models, and state of the art cellular interrogation methods; didactic course work designed to facilitate a better understanding of fundamentals of therapeutic product development, animal research, and biostatistics; and, regular attendance at vascular aging, genetics, and molecular biology conferences; and lastly exposure to teaching. Environment: The University of Utah is an ideal environment for Dr. Tuday's career development. This environment provides all the resources needed to complete the proposed studies during this K08 proposal. The University of Utah also provides a rich environment for formal and informal training in career development. Research: The central hypothesis of this research project is that age-related reductions in microRNA-181b expression levels results in the deregulation of pro-inflammatory pathways that ultimately result in increased large artery stiffness. It is known that microRNA-181b is beneficial in terms of vascular health and that levels decrease with age; we seek to understand these mechanisms. While many of the mechanisms of microRNA- 181b have been described, we contend that there are unstudied pathways influenced by microRNA-181b of significance as they relate to vascular health, specifically to vascular smooth muscle cells (VSMC). Finally, we hypothesize that chronic, VSMC specific, microRNA-181b overexpression can prevent the age-associated increases in large artery stiffness that ultimately preserve cardiovascular health.