# The proinflammatory functions of granzymes and their impact on endothelial inflammation/injury

> **NIH NIH R21** · GEORGETOWN UNIVERSITY · 2024 · $210,600

## Abstract

Project Summary
While antiretroviral therapy successfully suppresses HIV replication, immune activation and inflammation
persist, albeit at lower levels, and has been associated to as an important contributor of morbidity and
mortality in PWH. The clinical significance of immune activation is the evidence that demonstrates that HIV-
associated T cell immune activation and inflammation drive cardiovascular risk, independent of the traditional
risk factors, duration of antiretroviral treatment, and CD4 counts. Persistent HIV reservoirs are independently
associated with incident carotid plaque, and people with coronary artery atherosclerotic plaques show higher
levels of HIV DNA compared to those without disease. The molecular pathways by which HIV contributes to the
increased risk is largely unknown, and difficult the development of more targeted therapies.
CD8 T cell immune activation is associated with endothelial inflammation and dysfunction, and in this study, we
hypothesize that HIV-driven CD8 T cell immune activation promotes secretion of granzymes contributing to
vascular inflammation/injury. We will test this hypothesis by: Aim1. Granzymes expression regulation by memory
CD8 T cell subsets and virus-specific CD8 T cells recruited to the sites of vascular injury to define their
proinflammatory vs cytotoxic potential. Aim2. Granzyme expressing CD8 T cells enhance atherosclerosis
progression during infection. We will assess the extracellular contribution of granzymes and their impact in the
progression of a disease during infection.

## Key facts

- **NIH application ID:** 11013649
- **Project number:** 1R21AI186960-01
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Marta L. Catalfamo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $210,600
- **Award type:** 1
- **Project period:** 2024-07-22 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11013649

## Citation

> US National Institutes of Health, RePORTER application 11013649, The proinflammatory functions of granzymes and their impact on endothelial inflammation/injury (1R21AI186960-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/11013649. Licensed CC0.

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