Targeting immune cells to prevent aortic aneurysm progression and rupture.

Doctor Vivian Tran, La Trobe University

Postdoctoral Fellowship

Years funded: 2026 - 2028

AAA is a life-threatening condition where the abdominal aorta becomes inflamed and expanded, increasing the risk of rupture. It affects people >65 years old, with a higher incidence in men (7%) compared to women (2%). In Australia, AAA causes >3,500 hospital admissions and ~1,000 deaths annually. Many Australians remain undiagnosed until AAA rupture occurs, which is fatal in >80% of patients. Even if an AAA is detected early, there are no drug treatments available, and surgery is risky. Hence, new biomarkers and therapies to prevent AAA rupture are urgently needed.

Immune cell infiltration and inflammation are well-established features of AAA, both in humans and animal models. Building on this knowledge, and the clinical observation of elevated levels of proinflammatory interleukin-18 (IL-18) in AAA patients, we showed that the genetic deficiency of IL-18 completely eliminates AAA development and rupture in a mouse model. Furthermore, single-cell transcriptomic analyses of human and mouse AAA tissue revealed high numbers of gamma-delta (gd) T cells and identified them as a major cell type to express the receptor for IL-18, implicating them as likely mediators of IL-18’s AAA-promoting effects.

As a critical step towards clinical translation, I will determine whether IL-18 neutralising biologics or proprietary small molecular IL-18 inhibitors limit AAA develop and rupture in a mouse model. I will investigate whether IL-18 mediates its AAA-effects through gd T cells and define the disease pathways activated downstream of gd T cells in mouse models of AAA.

My work will form the basis for a highly feasible 2-year plan that will pave the way for similar studies in humans, which can predict disease risk, presence and severity. To reach this goal, I will continue to meet with our established advisory committee (metro/regional lived experience consumer panel and industry partners; Novartis and Bayer Pharmaceuticals) on a bi-monthly basis, ensuring rigorous progression of the project. The success of this project will produce drug interventions that halt/limit AAA development and a panel of biomarkers for early detection of AAA formation which can be integrated into the Heart Health checks. Additionally, I will leverage my long-standing connection with metro (founded Heart Camp; the first heart health literacy outreach program for young people and public seminars for World Heart Week) and regional (CAD Frontiers in Mildura) communities to disseminate this work and together, prevent the growing burden of cardiovascular disease for all Australians.