Hypertension (HTN) is a major risk factor for cardiovascular, cerebrovascular, and renal disease, and its prevalence is increasing, particularly among the elderly. While the pathophysiology of HTN is multi-factorial, two major contributors appear to be salt-sensitivity and activation of the immune system. The prevailing paradigm regarding salt-sensitive HTN is based upon increased plasma volume induced by intravascular sodium retention. Until recently, there was little consideration of the possibility that extravascular sodium stores may play a role. Through use of a novel non-invasive 23Na-magnetic resonance imaging (MRI) technique, we have demonstrated the presence of significant sodium accumulation in the skin and muscle. Experimental evidence indicates that these tissue sodium stores can trigger the immune system, particularly the T cells (Th17) that produce interleukin-17 (IL17). Activation of these T cells and the cytokines they produce, such as IL17, induces hypertension in animal models. Therefore, we postulate that tissue sodium-induced inflammation may contribute to the development and progression of HTN, particularly salt-sensitive HTN. In preliminary studies, we have shown that skin sodium content is associated with blood pressure, particularly in older individuals and men. We also found that circulating IL17 levels are higher in hypertensive compared with normotensive individuals. More definitive data from larger, community cohorts are needed. The Multi-Ethnic Study of Atherosclerosis is the ideal cohort in which to translate our preliminary findings, by testing the hypothesis that tissue sodium levels are positively associated with blood pressure and inflammation. We propose an ancillary study with the following specific aims: 1) To examine the association of tissue sodium with blood pressure in MESA participants. We will non-invasively quantify skin sodium concentration using 23Na-MRI and measure blood pressure in all eligible MESA participants at the Chicago, IL field center during exam 6 (2016-2018) and 2) To examine the association of tissue sodium with circulating cellular markers of inflammation. We will quantify the number and types of circulating immune cells, such as Th17 cells, among MESA participants who undergo MRI measurement of tissue sodium concentration.
|Effective start/end date||9/1/16 → 6/30/20|
- Vanderbilt University (VUMC 59440//5R01HL133860-04)
- National Heart, Lung, and Blood Institute (VUMC 59440//5R01HL133860-04)