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

项目摘要 候选人：Eric Tuday，医学博士，博士是一名助理教授，同时被任命为 犹他州大学心脏病学和弗吉尼亚州湖城转化生理学实验室。博士 Tuday的研究主要集中在miR-181 b表达对年龄相关性大血管病变发展的影响。 动脉僵硬Tuday博士的长期目标是独立领导一个由校外资助的实验室， 研究重点是衰老的血管生物学和解决与年龄有关的血管疾病。 职业发展：该奖项将通过建立在他现有的基础上， 心血管生理学培训。具体而言，Tuday博士将接受规划和 执行评估啮齿类动物整个血管和单个平滑肌健康的研究。职业 发展计划概述了一个协调的努力，以培养候选人的领域，包括：血管生物学的 衰老;与病理状态、动物遗传模型和 艺术细胞审讯方法;教学课程工作，旨在促进更好地理解 治疗产品开发，动物研究和生物统计学的基础知识;以及，定期出席 在血管老化，遗传学和分子生物学会议;最后接触教学。 环境：犹他州大学是Tuday博士职业发展的理想环境。这 环境提供了在K 08提案期间完成拟议研究所需的所有资源。 犹他州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，与年龄相关的microRNA-181 b减少 表达水平导致促炎途径的失调，最终导致增加的 大动脉僵硬。众所周知，microRNA-181 b在血管健康方面是有益的， 随着年龄的增长而减少;我们试图了解这些机制。虽然microRNA的许多机制- 181 b已经被描述，我们认为有未研究的途径受microRNA-181 b的影响， 重要性，因为它们涉及血管健康，特别是血管平滑肌细胞（VSMC）。最后我们 假设慢性VSMC特异性microRNA-181 b过表达可以预防年龄相关性 增加大动脉硬度，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.