The Impact of Modern Industrialized Dietary Sodium Intake on the Plasma Proteome.

BACKGROUND

High dietary sodium intake is associated with cardiovascular disease. We investigated the influence of sodium intake on the plasma proteome.

METHODS

Prospectively recruited normotensive participants underwent 2 controlled dietary sodium interventions to evaluate hormonal and proteomic (1,512 proteins) changes: sodium-restriction resembling ancestral hunter-gatherer intake (~10 mEq/day, ~230 mg/day) and sodium-loading resembling modern industrialized intake (~200 mEq/day, ~4,600 mg/day). Twenty-four hour urine collections were obtained after each diet. Plasma proteomic changes were assessed with correction for false discovery.

RESULTS

Participants achieved a 24-h urinary sodium excretion of 16 mEq/L when sodium-restricted and 249 mEq/L when sodium-loaded. Thirty-eight proteins displayed statistically significant changes with 15 additional proteins exhibiting notable trends that did not reach statistical significance. The most apparent changes were increases in proteins related to fibrosis and the extracellular matrix (ECM) when sodium-loaded, whereas sodium-restriction increased proteins related to immune/inflammatory pathways and the renin-angiotensin system (RAS)-kallikrein-kinin system (KKS)-complement pathway. NT-proBNP, FUMH (fumarate hydratase), LKHA4 (leukotriene A(4) hydrolase), COFA1 (collagen alpha-1(V) chain), COF2 (cofilin-2), BMP-4, and TGF-β RIII had the greatest increases when sodium-loaded, whereas renin, thrombin, apo A-1 (apolipoprotein A-1), FABPA (fatty acid binding protein), and LEAP-1 (hepcidin) had the greatest increases when sodium-restricted.

CONCLUSIONS

When compared to a sodium-restricted diet resembling ancestral intake, the modern industrialized dietary sodium intake increased proteins related to fibrosis and the ECM, and decreased proteins related to the RAS, KKS, immunity, and inflammation. These findings in normotensive people provide an atlas of proteomic changes, and biological pathways, that may contribute to hypertension and other sodium-related disorders.