# The role of soluble prorenin receptor in hypertension associated with obesity

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $380,765

## Abstract

PROJECT SUMMARY/ABSTRACT
The epidemic of obesity, currently affecting more than 36.5% of the population in the United
States, has contributed to a rise in the prevalence of hypertension. We recently found that
obesity stimulated the secretion of the soluble form of the prorenin receptor (PRR), sPRR, into
plasma. While examining sPRR protein concentrations in tissues, we found an increase of
sPRR protein levels in the liver, the adipose tissue and the kidney of control mice fed a high fat
diet compared to mice fed a low fat diet. New preliminary data showed that the infusion of a
recombinant mouse sPRR in mice fed a standard diet activated local and circulating RAS by
increasing renal cortical angiotensinogen (AGT) and circulating renin levels. Consistent with
those results, our new results demonstrated that elevated plasma sPRR in adipose PRR KO
mice is associated with an increase of cortical angiotensin II levels in the kidney. Urinary
vasopressin levels also increased significantly in these mice. Together with our prior work, these
results raise the possibility that sPRR regulates the renin angiotensin system (RAS) and body
fluid volume. To test this idea, 3T3-L1 cells and human HepG2 cells were incubated with
increased concentration of recombinant mouse sPRR. We found that sPRR increased the
expression of AGT gene in 3T3-L1 cells and the secretion of AGT in the media of human
HepG2. In addition, the incubation with our sPRR neutralizing antibody decreased AngII levels
in the media of 3T3-L1 cells. Because sPRR infusion in mice increased plasma renin levels, we
also investigated whether sPRR regulated the expression of renin in kidney. Interestingly, we
found that sPRR binds to the promoter of the renin gene. Thus, we propose that obesity
stimulates sPRR production leading to hypertension through a mechanism that involves the
activation of the RAS and increases AVP. We will test the hypothesis that tissue-derived sPRR
mediates angiotensin II-induced hypertension associated with obesity, likely by amplifying the
local AGT and renin response and increases urinary AVP. We will also investigate whether
blocking sPRR can be used as a treatment for hypertension associated with obesity. Outcomes
will demonstrate whether obesity is regulated through a previously unrecognized pathway
represented by upstream control of RAS and AVP by sPRR. Our studies point to a unique
functional role for sPRR in hypertension associated with obesity.

## Key facts

- **NIH application ID:** 9962483
- **Project number:** 5R01HL142969-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Frederique Yiannikouris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,765
- **Award type:** 5
- **Project period:** 2018-07-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962483

## Citation

> US National Institutes of Health, RePORTER application 9962483, The role of soluble prorenin receptor in hypertension associated with obesity (5R01HL142969-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9962483. Licensed CC0.

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