Orthopedic surgery changes aortic valve composition in ApoE-/- mice

In atherosclerotic cardiovascular disease (ASCVD), acute systemic inflammatory insults such as infections or major surgery are known to trigger cardiovascular events. However, it remains unclear whether such systemic triggers also modulate local inflammatory and degenerative processes within the aortic valve (AV). We therefore investigated the effect of orthopedic surgery on AV remodeling in an atherosclerosis-prone setting.

ApoE-/- mice subjected to orthopedic surgery, ApoE-/- controls, and non-atherosclerotic controls were analyzed at 5 and 15 days post-intervention. AVs were assessed for valve thickness, fibrosis, glycosaminoglycans (GAGs), lipid accumulation, calcification, iron deposition, and inflammatory cell infiltration.

Atherosclerotic mice exhibited degenerative AV changes compared to non-atherosclerotic controls. Orthopedic surgery did not affect valve thickness or inflammatory cell infiltration, but induced compositional changes, including increased GAG content at day 5 (56.7 vs. 27.3; p = 0.016), a a higher fibrotic area at day 15 that did not reach statistical significance (41.3 vs. 24.9; p = 0.068), and reduced estimated lipid-rich area at day 5 (11.3 vs. 37.3; p = 0.008). No differences were observed in calcification or iron deposition.

Orthopedic surgery induces early compositional remodeling of atherosclerotic aortic valves without increasing inflammatory cell infiltration or valve thickening. These findings suggest that orthopedic surgery induces compositional remodeling of the AV in an atherosclerotic setting. Although inflammatory cell infiltration was not increased at the examined time points, the underlying molecular mechanisms were not investigated. Therefore, systemic inflammatory mediators may contribute to these changes, but this remains to be established.