ABSTRACT Nearly half of U.S adults have hypertension (HTN), a leading cause of the cardiovascular disease (CVD). HTN that develops earlier in life contributes to the early development of end-organ damage, thereby increasing the risk of cardiovascular mortality compared to later-onset HTN. Multiple studies provide evidence for the hypothesis that environmental factors in utero program patterns of fetal and infant growth that result in increased susceptibility to HTN later in life. Vitamin D (VD) deficiency is highly prevalent during pregnancy and has been linked to an increased risk of HTN during childhood. We previously found that macrophage-specific deletion of the VD receptor during early embryogenesis induced HTN by two mechanisms: a) renal-dependent by stimulating the secretion of miR106b to drive JG cell renin production and b) renal-independent by increased macrophage renin production and secretion. Additional studies in rodent models support the role of maternal VD deficiency in developing HTN and chronic inflammation via epigenetic mechanisms. In this proposal, we present preliminary data indicating for the first time that HTN is transplantable by immune cells. Hematopoietic stem cells (HSCs) from fetuses exposed to VD deficiency in utero can permanently transfer HTN to VD-sufficient adult mice. Vitamin D deficiency epigenetically suppresses Jarid2 expression and activates the Mef2/PGC1α pathway in HSCs, which persists in recipient bone marrow, resulting in macrophage renin and miR-106b secretion, both of which represent novel mechanisms by which immune cells contribute to the development of HTN. In humans, we found that this immune cells program causing HTN is preventable in children monocytes from the VDAART trial by antenatal 4400 IU/day of VD supplementation. Importantly, children from VD-supplemented mothers have decreased brachial-systolic blood pressure (BP). Thus, we hypothesize that VD supplementation early in pregnancy prevents epigenetic suppressi