# Toll-like receptor 9 activation by mitochondrial DNA causes vascular injury in hypertension

> **NIH NIH P01** · AUGUSTA UNIVERSITY · 2020 · $380,000

## Abstract

PROJECT SUMMARY P1, WEBB
Toll-like receptor 9 activation by mitochondrial DNA causes vascular injury in hypertension
Hypertension affects over 75 million U.S. adults and plays a major role in the end organ damage commonly
seen with cardiovascular diseases, including stroke, coronary artery disease, and ischemic nephropathy. Our
proposal provides a new paradigm whereby activation of the innate immune system via mitochondrial DNA
(mtDNA) leads to increased vasoconstriction, reduced vasodilation and vascular remodeling in hypertension.
Understanding this mechanism may assist in the development of new drugs that target the immune system to
treat vascular dysfunction and prevent the progression of hypertension. The research will be guided by the
novel hypothesis that in hypertension, exaggerated vascular and tissue cell death give rise to mtDNA that
trigger the innate immune response via Toll-like receptor 9 (TLR9) causing vascular inflammation,
vasoconstriction, endothelial dysfunction and vascular remodeling. A rat model of hypertension
[spontaneously hypertensive rat (SHR)] will be used and we will test our hypothesis by accomplishing three
specific aims: 1) test the hypothesis that pharmacological inhibition of cell necrosis attenuates the
development of vascular dysfunction in hypertension; 2) test the hypothesis that activation of TLR9 signaling
causes endothelial dysfunction, potentiates vasoconstriction and contributes to arterial stiffening; and 3) test
the hypothesis that mtDNA contributes to the development and maintenance of hypertension. The proposed
studies, integrating physiological, pharmacological, biochemical, molecular and cellular techniques, will help to
better understand the effects of blood pressure on vascular function, as well as the contribution of abnormal
TLR9 activation to vascular dysfunction characteristic of hypertension.

## Key facts

- **NIH application ID:** 9859435
- **Project number:** 5P01HL134604-04
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** R Clinton Webb
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,000
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859435

## Citation

> US National Institutes of Health, RePORTER application 9859435, Toll-like receptor 9 activation by mitochondrial DNA causes vascular injury in hypertension (5P01HL134604-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9859435. Licensed CC0.

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