Extracellular vesicles and atherosclerotic peripheral arterial disease

Atherogenesis involves a complex multifactorial process including chronic inflammation that requires the participation of several cell types and molecules. In addition to their role in vascular homeostasis, extracellular vesicles also appear to play an important role in atherogenesis, including monocyte transmigration and foam cell formation, SMC proliferation and migration, leukocyte transmigration, and thrombosis. Peripheral arterial disease, a major form of peripheral vascular disease, is characterized by structural or functional impairment of peripheral arterial supply, often secondary to atherosclerosis. Elevated levels of extracellular vesicles have been demonstrated in patients with peripheral arterial disease and implicated in the development of atherosclerosis within peripheral vascular beds. However, extracellular vesicles also appear capable of delivering cargo with atheroprotective effects. This capability has been exploited in vesicles engineered to carry content capable of neovascularization, suggesting potential for therapeutic angiogenesis. This dual capacity holds substantial promise for diagnosis and therapy, including possibly limb- and life-saving options for peripheral arterial disease management.