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

点击翻译按钮获取中文摘要

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.