# Vitamin D Deficiency, Insulin Resistance and Cardiovascular disease

> **NIH HL R01** · WASHINGTON UNIVERSITY · 2026 · $728,824

## Abstract

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

## Key facts

- **NIH application ID:** 11392902
- **Project number:** 5R01HL094818-13
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Carlos  Bernal-Mizrachi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $728,824
- **Award type:** 5
- **Project period:** 2010-04-15T00:00:00 → 2027-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11392902

## Citation

> US National Institutes of Health, RePORTER application 11392902, Vitamin D Deficiency, Insulin Resistance and Cardiovascular disease (5R01HL094818-13). Retrieved via AI Analytics 2026-05-20 from https://api.ai-analytics.org/grant/nih/11392902. Licensed CC0.

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