Applications of Extracellular Vesicles in Abdominal Aortic Aneurysm

Abstract

Abdominal aortic aneurysm (AAA) is a localized expansion of the abdominal aorta which can lead to lethal complication as the rupture of aortic wall. Currently there is still neither competent method to predict the impending rupture of aneurysm, nor effective treatment to arrest the progression of small and asymptomatic aneurysms. Accumulating evidence has confirmed the crucial role of extracellular vesicles (EVs) in the pathological course of AAA, acting as important mediators of intercellular communication. Given the advantages of intrinsic targeting properties, lower toxicity and fair stability, EVs show great potential to serve as biomarkers, therapeutic agents and drug delivery carriers. However, EV therapies still face several major challenges before they can be applied clinically, including off-target effect, low accumulation rate and rapid clearance by mononuclear phagocyte system. In this review, we first illustrate the roles of EV in the pathological process of AAA and evaluate its possible clinical applications. We also identify present challenges for EV applications, highlight different strategies of EV engineering and constructions of EV-like nanoparticles, including EV display technology and membrane hybrid technology. These leading-edge techniques have been recently employed in multiple cardiovascular diseases and their promising application in the field of AAA is discussed.

Biodelivery of therapeutic extracellular vesicles: should mononuclear phagocytes always be feared?

“…Similarly to other new therapeutics, EVs’ biodistribution studies focus on validation of pharmacokinetic parameters, including half-lives of distribution and elimination phases ( Kang et al, 2021 ). The rapid clearance of therapeutic EVs, resulting in their short half-life in circulation, is one of the main difficulties when adapting them to therapy ( Esmaeili et al, 2022 ; Lu et al, 2022 ). Accordingly, some researchers point to the relatively short half-life of EV in various tissues, estimated at 30 min or less ( Lai et al, 2014 ; Ronquist, 2019 ), while others note the time-dependent changes in the circulation and biodistribution of administered EVs, as recently analyzed by Kang et al (2021) .…”

The future for the therapeutics of abdominal aortic aneurysm: engineered nanoparticles drug delivery for abdominal aortic aneurysm

“…To address these issues, natural EVs can be further modified by tissue engineering approaches. For instance, adding targeting ligands (EV display technology), and cell membrane fusion techniques could improve their targeting and circulatory delivery efficiency (Luk and Zhang, 2015;Witwer and Wolfram, 2021;Lu et al, 2022), as shown in Figure 6.…”

“…However, there are many problems with EV display technology, for example, the process is very labor-intensive and time-consuming, and the added functional membrane proteins are sometimes degraded by proteases of cells or body fluids, losing their targeting properties. Enhancing the stability and persistence of the targeting peptide is very meaningful for the further development of EV display technology (Lu et al, 2022). The cell membrane fusion technology is also getting more and more attention, which can fuse EV membranes with the cell membranes of many kinds of cells in biomedical applications.…”

Identification of biomarkers for abdominal aortic aneurysm in Behçet's disease via mendelian randomization and integrated bioinformatics analyses

“…2 Abdominal aortic aneurysm (AAA) is distinguished by the infiltration of immune cells, heightened proteolytic activity and persistent degradation of extracellular matrix constituents, including collagen, elastin, fibronectin and laminin, thus expanding the aortic wall. 3 Although the involvement of AAA in BD is rare, it can be associated with severe consequences. AAA is characterised by progressive aortic dilation that may result in a potentially lethal rupture.…”