# Role of endothelin in hypertension-mediated inflammation and end-organ damage

> **NIH NIH K01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $152,627

## Abstract

PROJECT SUMMARY
Extensive evidence demonstrates that individuals that regularly consume high salt diet have a greater risk of
developing cardiovascular diseases (CVD) compared to individuals on low salt diet. Moreover, dietary
consumption of high salt and the associated inflammation have critical roles in the development of CVD, such
as hypertension. Particularly, T cells are intimately linked to the development of hypertension. However there is
a gap in our knowledge of the mechanisms involved in salt-mediated T cell activation, end-organ damage and
CVD risk.
Levels of endothelin-1 (ET-1), a potent vasoactive peptide, are elevated after high salt consumption. Renal
inflammation is one of the hallmarks of salt-sensitive hypertension, and ET-1 is known to exert pro-inflammatory
actions in renal tissue. In fact, human T cells express ET-1 receptors (ETA and ETB) on their surface and are
activated by ET-1 in vitro. Recent reports demonstrate that high salt induces production of pro-inflammatory
cytokines by T cells. Despite the many studies demonstrating that the renal ET-1 system is an important
contributor to increased blood pressure, inflammation and kidney damage during high sodium intake, the
molecular mechanisms by which ET-1 mediates these effects remain obscure. Further, the involvement of ET-1
in renal T cell activation and target organ damage during salt-dependent hypertension needs investigation.
High salt consumption increases ET-1 production by several cellular sources in the kidney, although the cellular
source of ET-1 mediating renal T cell activation and differentiation during high salt remains unclear.
This proposal aims to elucidate novel molecular pathways involved in the control of the renal pathophysiology
associated with increased blood pressure. This proposal will test that 1) activation of the ET-1/ETA axis leads to
kidney T cell activation during salt-sensitive hypertension and results in salt-induced kidney damage and CVD
risk, and 2) elevated vascular endothelium-derived ET-1 is responsible for the kidney damage observed during
high salt consumption.
With the help of my mentor and scientific advisory team, I will continue on the path toward my long-term goal of
developing a strong and independent research program at the intersection of immunology and cardio-renal
physiology, with the ultimate goal of translating this knowledge to improve human health. If awarded, this K01
award will help me to achieve extra training to become a successful basic science investigator in the field of
cardio-renal physiology.

## Key facts

- **NIH application ID:** 9857658
- **Project number:** 5K01HL145324-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Carmen De Miguel
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $152,627
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857658

## Citation

> US National Institutes of Health, RePORTER application 9857658, Role of endothelin in hypertension-mediated inflammation and end-organ damage (5K01HL145324-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9857658. Licensed CC0.

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