# Leukocyte trafficking in thoracic grafts

> **NIH VA I01** · ST. LOUIS VA MEDICAL CENTER · 2022 · —

## Abstract

Project Summary / Abstract
Cardiovascular disease and heart failure are highly prevalent among the veteran population. Cardiac
transplantation remains a preferred therapy for patients who suffer from end-stage heart failure.
However, outcomes after heart transplantation are adversely impacted by primary graft dysfunction, a
consequence of ischemia reperfusion injury. Primary graft dysfunction causes immediate tissue
damage and can also augment adaptive immune responses that trigger graft rejection. Currently, there
are no effective therapies for primary graft dysfunction after heart transplantation and the management
of these patients is mostly supportive. Our laboratory has developed intravital imaging platforms that
has allowed us to visualize the infiltration of leukocytes into murine heart grafts in real time. Through
these approaches we have uncovered cellular and molecular cues that regulate the trafficking of
neutrophils and monocytes, innate immune cells that are known to mediate tissue damage, into
transplanted hearts. Our findings raise the intriguing prospect that targeting immune pathways and cell
populations within the donor graft can control the initial immune response following heart
transplantation. During the previous funding period we have discovered that ferroptosis, a non-
apoptotic form of cell death mediates the early inflammatory response after reperfusion of heart grafts.
We have reported that graft endothelial cells and tissue-resident CCR2+ macrophages play critical and
complementary roles in driving the recruitment of neutrophils to the transplanted heart. Now we have
generated preliminary data showing that additional donor immune cell populations and signaling
pathways regulate leukocyte recruitment to cardiac grafts. In this proposal, we will use state-of-the-art
techniques including intravital two-photon microscopy, new positron emission tomography probes,
single cell RNA sequencing and novel murine strains to perform studies that will define the role of donor
non-classical monocytes (Aim 1) and TREM-1/3 signaling (Aim 2) in promoting inflammatory
responses after reperfusion of ischemic heart grafts. Our studies will lay the foundation for novel
therapies that will improve outcomes for heart transplant recipients and patients who suffer from
myocardial ischemia reperfusion injury due to other conditions.

## Key facts

- **NIH application ID:** 10370119
- **Project number:** 2I01BX002730-06A1
- **Recipient organization:** ST. LOUIS VA MEDICAL CENTER
- **Principal Investigator:** Daniel Kreisel
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2022-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370119

## Citation

> US National Institutes of Health, RePORTER application 10370119, Leukocyte trafficking in thoracic grafts (2I01BX002730-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10370119. Licensed CC0.

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