Title of project

Plasmalemma Vesicle-Associated Protein in the Abdominal Aortic Aneurysm Pathogenesis

Abstract

Abdominal aortic aneurysm (AAA) is an asymptomatic chronic vascular disease characterized by an abdominal aorta diameter exceeding 3 cm. AAA can lead to aortic rupture, which has a mortality rate of 85-90%, leading to 150,000-200,000 deaths annually. Currently, there are no pharmacological treatments for AAA and the standard care for AAAs with a diameter above 5.5 cm is either stenting or surgical repair. Although the underlying pathogenesis of AAA progression and rupture remains unclear, factors such as elevated blood pressure and chronic inflammation of the aortic wall have been implicated. Emerging evidence suggests that dysfunction and leakiness of the aortic wall microvasculature, the vasa vasorum, plays a causal role in degeneration of the aortic wall during AAA development.

Preliminary studies by the Ravnskjaer lab show strong induction of the protein Plasmalemma vesicle-associated protein (PLVAP) in both human and murine AAA. Single-cell transcriptomic data analysis show increased PLVAP expression specifically in the human AAA endothelium. PLVAP has previously been associated with microvascular permeability, and these findings may implicate PLVAP in the pathogenesis of AAA.

To elucidate the role of PLVAP in AAA pathogenesis, we will further study both human and murine AAA and investigate interactions between the vasa vasorum, stromal cells, and immune cells. Functional insights into endothelial PLVAP induction and vasa vasorum leakiness in AAA may be of potential use in microvasculature-directed intervention of AAA and beyond.