Aortic aneurysm disease, a condition often referred to as the “silent killer,” continues to be one of the most underdiagnosed conditions in America, affecting up to 5 million Americans. Most patients are unaware they have the condition and can suffer from catastrophic complications, specifically aortic rupture, and dissection. To this date, there is no biomarker for the detection, surveillance, and monitoring of aortic aneurysm disease. Development of an aortic aneurysm biomarker would have a profound impact in the treatment of the disease.

Exosomes are cell-specific nanoparticles released into peripheral blood by many types of cells. When cells are injured or diseased, their exosome protein and RNA contents are conditionally altered. Studies have shown that aneurysm development leads to distinct molecular changes in the aortic endothelial cells, which are cells that line the inner walls of blood vessels. We hypothesized that the injury of endothelial cells caused from aortic aneurysm disease would be reflected in the exosomes they release. Our laboratory developed novel methods to isolate and characterize aortic endothelial exosomes as well as their protein and RNA cargoes from peripheral blood samples as potential biomarkers of aortic aneurysm disease.

Our laboratory matched 40 subjects with ascending aortic aneurysms with 40 control subjects and isolated endothelial exosomes from blood samples. Their cargoes were analyzed for expression levels of two known endothelial markers: VE-cadherin and ICAM. Levels of both markers were significantly decreased in aneurysm subjects.

Aneurysm development is strongly associated with increased levels of proteins called metalloproteinases (MMPs) in aortic aneurysm tissue. We found that MMP7, MMP9, and MMP14 protein and mRNA levels were significantly elevated in endothelial exosomes from aneurysm subjects, with levels of MMPs in endothelial exosomes correlating with increased levels noted in aneurysm tissue. This data demonstrates that endothelial exosome profiles hold promise as novel biomarkers of aortic aneurysm disease.