PROJECT SUMMARYHeart failure (HF) is a growing, morbid, and costly public health problem. Consequently, there is increasingrealization for the importance of early detection and prevention. Preliminary data suggests a meta-organismalpathway involving formation of trimethylamine N-oxide (TMAO) is a direct contributor to heart failuresusceptibility and adverse prognosis. The novel pathway involves a complex interplay between chronic dietaryexposure of specific dietary nutrients, gut microbe metabolism of these nutrients using specific microbialenzymes, and then host hepatic metabolism of the microbial waste product, ultimately producing a biologicallyactive compound, TMAO. Preliminary studies show TMAO adversely influences myocardial function andpromotes both myocardial fibrosis and heart failure phenotype. We propose to examine the role of specificchronic dietary exposures alternative to sodium in risk for adverse cardiac remodeling and heart failure, and tounderstand their potential mechanistic underpinnings. We will examine the role of gut microbes in heart failuresusceptibility, and specific microbial enzyme systems in this process. Finally, we will explore the potentialefficacy of therapeutic dietary approaches targeting this pathway for the prevention and treatment of heartfailure. Successful completion of the proposed studies should provide both important mechanistic insights intoa new pathway that contributes to heart failure development and progression, as well as develop noveldiagnostic tests and therapeutic approaches for the treatment of heart failure.
|Effective start/end date||7/1/16 → 4/30/20|
- National Institutes of Health: $785,852.00