# Immune injury as a driver for the development of ascending aortic aneurysms and dissections

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $608,729

## Abstract

Abstract
Acute aortic dissection, particularly the type A dissection (AAD), is a life-threatening condition. Currently, there
are no effective measures to prevent its onset and progression. A major barrier to satisfy these critical, unmet
clinical needs is the poor understanding of the mechanisms that drive AAD development. AADs usually occur in
aortas suffering progressive aneurysmal degeneration. However, compelling clinical evidence suggests that
AADs and aortic aneurysms precede through distinct biological pathways. Yet, uncoupling these pathways has
been a challenging task due to the silent onset of aortic dissections in patients coupled with a lack of animal
models capable of mimicking the development of AAD reliably. To address this issue, we created two novel
mouse AAD models, termed as “aortic tear model” and “aortic rupture model”, respectively. The “aortic tear
model” develops spontaneous aortic tears with few ruptures in mildly dilated ascending aortas, whereas the
“aortic rupture model” features acute aortic dissections with a high rate (40%) of aortic rupture in the first week.
Using these models, we tested the long-standing, but unproved, hypothesis—disorders of immune response
promote AAD formation. We found that 1) development of aortic tears is paralleled with an increased CD4+ T-
cells and CD19+ B-cells in the AAD tissue as well as in the peripheral blood; 2) Th2 polarization via adoptive
transfer of ex vivo expanded Th2 cells or neutralization of the Th1 signature cytokine interferon gamma (INFγ)
exaggerates AAD dilation; 3) complement components are upregulated and deposited in the medial layer of
AADs; and 4) genetic shifting of T-cell-mediated immune response to a Th2 prominent immunity dramatically
provokes aortic rupture (>90% in four weeks). These novel findings led to an overall hypothesis that skewing of
the inflammatory response in the aneurysmal aortic wall to type 2 immunity promotes AAD development. In this
project, we will use genetic, adoptive cell transfer, and pharmacological approaches to evaluate the role of T-
cells, B-cells, and complement system in regulating AAD development, with profile of immune cell subsets and
cytokine milieu characterized to understand the cellular and molecular events engaged in promoting AAD
formation. Critical findings will be validated for their implication across different mouse models, and more
importantly, their relevance to human AAD development. Completion of this project will lay a solid foundation for
future studies to develop immunotherapies to prevent AAD formation.

## Key facts

- **NIH application ID:** 10029084
- **Project number:** 1R01HL153545-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Zhihua Jiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $608,729
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10029084

## Citation

> US National Institutes of Health, RePORTER application 10029084, Immune injury as a driver for the development of ascending aortic aneurysms and dissections (1R01HL153545-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10029084. Licensed CC0.

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