Title of project

Regulation of phosphaturic hormones by dietary K+ and its relevance to cardiovascular and bone health

Abstract

High blood pressure is a growing global health problem, affecting more than 1.2 billion people. Hypertension is a major modifiable risk factor for cardiovascular disease, diabetes, kidney failure and premature death. Although genetic susceptibility and obesity are major contributors to the onset of hypertension, the underlying causes of many forms of hypertension are largely unknown and current treatment strategies are suboptimal. High dietary sodium (Na) consumption is often considered a primary culprit for high blood pressure (BP), but growing evidence indicates that low potassium (K) consumption has an equally important role; with both dietary conditions altering activity of the renin-angiotensin-aldosterone (RAAS) system, volume homeostasis and BP. Intriguingly, emerging evidence suggests that alterations in dietary intake of Na and K also affect phosphate (Pi) and calcium (Ca) balance, which influences cardiovascular and bone health. Increased dietary Na leads to adverse cardiovascular and bone mineral density (BMD) outcomes, whereas an increase in dietary K improves BMD. The molecular mechanisms for how increased dietary K intake has positive effects on bone and cardiovascular health remains unknown. In this project, the overarching goal is to use a series of in vivo mouse models and ex vivo primary cultures to determine if various endocrine factors such as active vitamin D (1,25(OH)2D), parathyroid hormone (PTH) or fibroblast growth factor-23 (Fgf23) mediate crosstalk between dietary K intake, the renin-angiotensin-aldosterone system, and bone-cardiovascular health. As emerging data point towards a role for disturbances in phosphate metabolism and Fgf23 in diabetes (diabetic ketoacidosis), the mechanisms uncovered have additional translational potential.