# Mineralocorticoid receptor mediates vascular stiffness via dysregulated immunity in perivascular adipose tissue

> **NIH NIH K08** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $167,702

## Abstract

Project summary
My research is focused on the interactions between mineralocorticoid receptor (MR) signaling in perivascular
adipose tissue (PVAT), dysregulation of immunity and vascular dysfunction in the setting of high-fat high-
fructose diet (Western Diet [WD]). WD leads to insulin resistance. Importantly, insulin resistance leads to
aggressive cardiovascular disease in females. I hypothesize that in females, WD-induced insulin resistance
results in loss of T regulatory (Treg) function leading to macrophage MR activation and subsequent M1
polarization in PVAT. Further, I hypothesize that these events increase vascular stiffness via activation of
Tissue transglutaminase-2 (TG2), in part, through oxidative stress and decreased bioavailable nitric oxide
(NO). To test my hypothesis, specific Aim 1 is to determine the effect of MR activation in PVAT macrophages
on the pathogenesis of vascular stiffness as it relates to impaired Treg function and M1 macrophage
polarization. Myeloid-specific MR knockout (MyMRKO) male and female mice will be treated with a WD or
aldosterone and we will measure aortic stiffness. In PVAT, we will measure macrophage polarization and
inflammation. We will measure cellular stiffness in primary endothelial cells (EC) and vascular smooth muscle
cells (VSMC) cultured in PVAT-conditioned media from each cohort. In Specific Aim 2, we will determine the
role of Tregs on PVAT macrophage polarization and aortic stiffness. In this set of experiments, we will use
adoptive Treg transfer from male and female C57Bl/6J mice fed a normal diet to the mice treated with WD or
slow pressor doses of aldosterone. We will measure macrophage polarization, inflammation and aortic
stiffness, along with EC/VSMC stiffness measurement in PVAT-conditioned media. I have assembled a team
of mentors and collaborators that will guide me throughout this project and promote my transition as an
independent researcher. My career development plan has an initial training period (years 1-3) in which I will
complete the proposed work, and a transitional period (years 4-5) during which I will focus on an R01 proposal.
My mentoring team has the necessary infrastructure, expertise and resources and my institution will provide
the necessary support to enable me successfully achieve my goals. My intermediate goal is to successfully
complete the work I propose. My ultimate goal is to establish a distinct line of work addressing the mechanisms
by which MR activation and dysregulated immunity lead to vascular disease.

## Key facts

- **NIH application ID:** 9843599
- **Project number:** 5K08HL132012-04
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Guido Lastra
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $167,702
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843599

## Citation

> US National Institutes of Health, RePORTER application 9843599, Mineralocorticoid receptor mediates vascular stiffness via dysregulated immunity in perivascular adipose tissue (5K08HL132012-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9843599. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*