# The role of angiotensin-(1-7) in hypertension and hypertension-induced heart and kidney damage

> **NIH NIH K23** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $156,600

## Abstract

ABSTRACT
Hypertension is a leading cause of death and originates in childhood. Hypertension in childhood is common,
causes heart and kidney injury, and predicts adult hypertension, but poor treatment response occurs in 50% of
children and increases the risk of heart and kidney injury. Predicting treatment response may improve health
throughout one’s life, but no predictors currently exist. The reasons for poor treatment response and how
children develop heart and kidney injury are not fully understood; these gaps limit patient care. Preliminary
data suggest changes to angiotensin-(1-7), uric acid, and klotho may be critical to the early development of
hypertension and organ injury. However, this has not been studied in pediatric hypertension. The goal of this
K23 is to initiate a mentored research project and training plan to a) establish a foundation of clinical evidence
of angiotensin-(1-7) in pediatric hypertension and b) obtain training, education, experience, and data needed to
transition to an independent patient-oriented research career focused on addressing gaps between basic
science and clinical research in the mechanisms of hypertension in order to prevent and treat cardiovascular
disease across the lifespan. This prospective cohort study of children aged 5 to 17 years with hypertension will
measure angiotensin-(1-7), uric acid, and klotho in blood and urine and use novel causal inference methods to
analyze their relationships to blood pressure and measures of heart and kidney injury. The specific aims are:
i) determine if angiotensin-(1-7) differs in hypertension subjects vs. normotensive controls and mediates effect
of blood pressure lowering on heart and kidney injury in subjects; ii) evaluate if angiotensin-(1-7) predicts
treatment response in subjects; and iii) determine if angiotensin-(1-7) mediates the relationships between uric
acid and heart injury and klotho and kidney injury in subjects. The central hypotheses are that 1) angiotensin-
(1-7) is lower in subjects vs. controls and mediates the effect of reduced blood pressure on improved outcomes
in subjects; 2) angiotensin-(1-7) predicts treatment response in subjects; and 3) angiotensin-(1-7) mediates the
associations of uric acid with heart injury and klotho with kidney injury in subjects. Results will lead to an
improved understanding of pediatric hypertension by identifying differences in how the disease progresses in
response to treatment and providing crucial evidence of how hypertension-related organ injury occurs. This will
improve patient care by defining new types of disease and informing new treatment strategies. The Candidate
is a tenure-track assistant professor with 75% protected time and research funds, equipment, and personnel
supported by the department and institution. The Candidate has a well-defined mentored learning plan that
provides training in large cohort studies, advanced statistics, assay and cellular mechanisms, and clinical
cardiovascular measures. ...

## Key facts

- **NIH application ID:** 10868656
- **Project number:** 5K23HL148394-05
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Andrew Michael South
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $156,600
- **Award type:** 5
- **Project period:** 2020-08-03 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868656

## Citation

> US National Institutes of Health, RePORTER application 10868656, The role of angiotensin-(1-7) in hypertension and hypertension-induced heart and kidney damage (5K23HL148394-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10868656. Licensed CC0.

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