Project: Nitrate reduction, Cardiovascular Health and the Oral Microbiome
University Association: UTHSC and Texas Therapeutics Institute
Collaborator Name: Nathan S. Bryan, Ph.D.
Dr. Bryan's research is dedicated to providing a better understanding of the interactions of nitric oxide (NO) and related metabolites with their different biological targets at the molecular and cellular level and the significance of these reactions for physiology and pathophysiology using systems biology approach. Attempts are made to identify what particular changes in NO-related signaling pathways and reaction products occur in disease states such as endothelial dysfunction, ischemia/reperfusion, tissue/cardiac protection, diabetes, atherosclerosis and inflammation with the aim of testing their amenability as biomarkers for diagnosis and/or treatment of specific disease, providing an interface between analytical biochemistry, physiology/pharmacology and medicine.
Current research is directed to understand the interactions of exogenous dietary nitrite/nitrate (NOx) on the endogenous NO/cGMP pathway and how perturbations in each system affect cardiovascular health. This involves mechanisms of nitrite transport and cellular uptake as well as mechanism of nitrite reduction back to NO and via direct NO-independent signaling actions of nitrite.
Work in Dr. Bryan's lab involves molecular biology and analytical biochemistry utilizing gas phase chemiluminescence and HPLC in multiple organ systems and blood. Much of the work involves in vivo characterization of NO/nitrite metabolism using a number of transgenic and knockout animal models of disease. Dr. Bryan and colleagues recently discovered that nitrite is a biologically active molecule which was previously thought to be an inert breakdown product of NO production. Since nitrite and nitrate are common constituents of many fruits and vegetables, changes in dietary habits may have profound effects on many diseases associated with NO insufficiency. NO insufficiency is a hallmark of a number of diseases including cardiovascular disease. The notion that nitrite can be recycled back to NO may serve as an alternative and compensatory mechanism of NO production and may serve as the endocrine mediator of NO signaling. Moreover, the direct signaling actions of nitrite may represent a novel NO independent pathway for nitrite.
If our current understanding is true, then an optimal diet may then consist of a sufficient supply of nitrite and nitrate for health and disease prevention. Understanding this pathway will provide the basis for new preventive or therapeutic strategies in diseases associated with NO insufficiency and new guidelines for optimal health.