High salt diet causes epigenetic modifications and suppresses endothelial progenitor cell function (1120.2)

Abstract

Endothelial progenitor cells (EPCs) are bone‐marrow derived cells that exhibit endothelial cell properties, promote neovascularization, and contribute to vascular homeostasis through autocrine and paracrine mechanisms. We describe for the first time how dietary salt negatively affects EPC function. EPCs were significantly decreased in the bone marrow of rats on a high salt diet (HSD, 4% NaCl) as compared to normal salt diet (NSD, 0.4% NaCl) rats. CD34, CD133, VEFGR2, and c‐Kit expression was similar between NSD and HSD EPCs. HSD EPCs had suppressed in vitro tube formation and were unable to restore angiogenesis following transplantation into a rodent model of limited angiogenesis (Sprague Dawley rats on a HSD). To identify molecular candidates that were altered by dietary salt, we preformed reduced representative bisulfite sequencing to analyze DNA methylation and we preformed mass spectrometry to identify differentially expressed protein targets. Analyses revealed increased methylation and suppressed protein expression of RET (proto‐oncogene tyrosine‐protein kinase receptor Ret) in HSD EPCs. Loss of RET expression causes thyroid tumor suppression and increased cell death providing a mechanistic explanation for HSD EPC reduced angiogenic efficacy. Overall high salt inhibits EPC angiogenic function through DNA methylation causing proteomic changes on the membrane.Grant Funding Source: HL‐082798