Efecto de la homeostasis y funcionalidad mitocondrial en el aneurisma de aorta abdominal y su modificación mediante la inhibición del factor XA por rivaroxabán

Abstract

Abdominal aortic aneurysm (AAA) is a the fifteenth most common cause of death in western countries. However, no effective pharmacological treatment is currently available to prevent AAA development or progression. A deep understanding of the pathogenesis of the disease is needed in order to developnew therapeutic targets. This pathogenesis of the AAA involves proteolytic degradation of extracellular matrix, vascular smooth muscle cells apoptosis, infiltration of chronic inflammatory cells and oxidative stress. Nevertheless, the specific cellular and molecular mechanisms involved in the formation, progression, and rupture of AAA are not fully understood yet. Mitochondria have a critical role in cellular energy metabolism and they are an important source of oxidative stress. Mitochondrial function has recently been associated to cardiovascular disease, including AAA, in different studies. Factor Xa (FXa) has pro-inflammatory and proteolytic effects on the vascular wall which are independent from prothrombin activation. Moreover, FXa can modify the expression of proteins involved in oxidative stress and energy metabolism. This activity could be mediated, at least partially, by mitochondrial dysfunction...