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

项目总结 候选人：Eric Tuday，医学博士，助理教授，兼任 犹他大学的心脏病学和弗吉尼亚州盐湖城的翻译生理学实验室。Dr。 Tuday的研究重点是miR-181b表达对年龄相关性大鼠发育的影响 动脉僵硬。Tuday博士的长期目标是独立领导一个由外部资助的实验室， 研究的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：该奖项将支持Tuday博士的职业发展，建立在他现有的基础上 心血管生理学方面的培训。具体地说，图代博士将接受广泛的规划和培训 执行评估啮齿动物整体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对候选人进行培训的协调努力： 衰老；与病理状态、动物遗传模型和疾病状态有关的分子通路的评估 ART细胞讯问方法；旨在促进更好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；以及定期参加 参加血管衰老、遗传学和分子生物学会议；最后参加教学。 环境：犹他大学是图代博士职业发展的理想环境。这 环境提供了在本K08提案期间完成拟议研究所需的所有资源。 犹他大学还为正式和非正式的职业发展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-181b减少 表达水平导致促炎途径的放松调控，最终导致增加 大动脉僵硬。已知microRNA-181b在血管健康和水平方面是有益的 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- 181b已被描述，我们认为存在未被研究的受microRNA-181b影响的通路。 由于它们与血管健康有关，特别是与血管平滑肌细胞(VSMC)有关，因此具有重要意义。最后，我们 假设慢性的，VSMC特异性的，microRNA-181b的过度表达可以防止与年龄相关的 大动脉僵硬增加，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.