# The Role of Vitamin D Deficiency-induced Macrophage Renin Angiotensin System Activation in the Development of Hypertension

> **NIH VA IK2** · ST. LOUIS VA MEDICAL CENTER · 2024 · —

## Abstract

RESEARCH STRATEGY: The objective of this proposal is to delineate the mechanisms by which macrophage
renin signaling contributes to the development of hypertension (HTN) associated with disrupted vitamin D (VD)
signaling. HTN is the most common chronic disease in the veteran population and associated with an increased
risk of cardiovascular disease and stroke. Despite our best efforts, many veterans have uncontrolled HTN,
highlighting the need for novel therapeutic strategies. Since VD deficiency is common among veterans,
associated with the development of HTN in humans, and promotes a pro-inflammatory macrophage phenotype,
we have focused on the mechanisms by which disrupted VD signaling contributes to the development of HTN.
We have found that macrophage renin secretion is stimulated by deletion of the VD receptor (VDR) in
macrophages (KODMAC). Transplantation of bone marrow from KODMAC mice into renin-null mice normalizes
blood pressure (BP) and restores circulating renin, highlighting the physiological relevance of macrophage renin
in regulating systemic BP. However, the role of local macrophage renin in driving HTN, as well as the
mechanisms governing macrophage renin transcription and the impact of macrophage-produced renin on
macrophage immune function are not known. The goal of this proposal is to test the hypothesis that
macrophage renin is a critical non-renal modulator of systemic HTN and inflammation in the setting of
disrupted VD signaling. Our Aims are to (1) determine the role of local macrophage renin in mediating the
development of HTN in murine models with disrupted macrophage VD signaling and (2) determine the
mechanisms associated with macrophage renin upregulation in the setting of disrupted VD signaling and its
effect on the macrophage function/secretome. The expected outcome of this work is to establish a new paradigm
by which impaired VD signaling functions as a major immunoregulatory program involved in systemic BP
regulation via increase macrophage renin production. We also expect that these findings will generate novel
therapeutic strategies for HTN management.
CANDIDATE/ENVIRONMENT: Dr. Kevin Bauerle is a Staff Physician in Endocrinology at the St. Louis VAMC
and Instructor in Medicine within the Division of Endocrinology at Washington University (WU). He completed
his M.D., Ph.D. training at the University of Colorado School of Medicine where he performed graduate studies
in Dr. Bryan Haugen's laboratory. Dr. Bauerle completed his residency in internal medicine at Beth Israel
Deaconess Medical Center and endocrinology fellowship at WU. He conducted his fellowship research with Dr.
Charles Harris, and currently works with his mentor Dr. Carlos Bernal-Mizrachi. Dr. Bauerle has gained
experience in metabolic phenotyping and VD signaling in immune cells and developed novel mouse models to
investigate the role of macrophage renin signaling in HTN. He now seeks to expand his expertise in immunology,
macrophage phenotyping, ...

## Key facts

- **NIH application ID:** 10804879
- **Project number:** 1IK2BX006205-01A1
- **Recipient organization:** ST. LOUIS VA MEDICAL CENTER
- **Principal Investigator:** Kevin T Bauerle
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-01-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10804879

## Citation

> US National Institutes of Health, RePORTER application 10804879, The Role of Vitamin D Deficiency-induced Macrophage Renin Angiotensin System Activation in the Development of Hypertension (1IK2BX006205-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10804879. Licensed CC0.

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