The high expression of elastases, observed in apelin deficient mice, could contribute to premature wear of elastic fibers and vascular stiffness.

Abstract Vascular stiffness is often the main cause of arterial hypertension and its complications including atherosclerosis, observed during obesity. However, the mechanisms leading to this rigidity or the preventing factors are misknown. We hypothesized that apelin, known for its beneficial effects on lipid, inflammatory, and vascular metabolism, could be a protective factor against vascular stiffness. We used mice deficient for the apelin gene (KO-APL) and compared with wild-type mice (WT) at the level of metabolic markers and inflammations of white adipose tissue (WAT), as well as aortic functional and anatomical parameters. KO-APL mice developed an inflammation associated with significant remodeling of WAT, in particular with the protease expressions such as neutrophil elastase or cathepsin S. From a vascular point of view, these same elastases are involved in the fragmentation of elastic fibers, explaining the increase in vascular velocity of pulse wave and arterial hypertension. Interestingly, univariate correlation analysis showed that the inflammation markers and protease expression of WAT were associated with remodeling of the vascular wall. Our results suggest that the modifications induced by the absence of apelin particularly in WAT, could facilitate the expression of elastases and the rupture of elastic fibers, necessary to maintain elastance. This discovery is fundamental because the synthesis of elastic fibers stops as of adolescence and is not renewed during the entire life of human. The preservation of these fibers is therefore critical in maintaining vascular homeostasis. Thus, Apelin could be an interesting therapeutic route to protect the premature wear of elastic fibers.