Orthopedic surgery increases atherosclerotic lesions and necrotic core area in ApoE−/− mice

Orthopedic surgery increases atherosclerotic lesions and necrotic core area in ApoE−/− mice

Fuijkschot, W.W.
Morrison, M.C.
van der Linden, R.
Krijnen, P.A.J.
Zethof, I.P.A.
Theyse, L.F.H.
Kleemann, R.
Niessen, H.W.M.
Smulders, Y.M.

2016

Background and aims Observational studies show a peak incidence of cardiovascular events after major surgery. For example, the risk of myocardial infarction increases 25-fold early after hip replacement. The acuteness of this increased risk suggests abrupt enhancement in plaque vulnerability, which may be related to intra-plaque inflammation, thinner fibrous cap and/or necrotic core expansion. We hypothesized that acute systemic inflammation following major orthopedic surgery induces such changes. Methods ApoE−/− mice were fed a western diet for 10 weeks. Thereafter, half the mice underwent mid-shaft femur osteotomy followed by realignment with an intramedullary K-wire, to mimic major orthopedic surgery. Mice were sacrificed 5 or 15 days post-surgery (n = 22) or post-saline injection (n = 13). Serum amyloid A (SAA) was measured as a marker of systemic inflammation. Paraffin embedded slides of the aortic root were stained to measure total plaque area and to quantify fibrosis, calcification, necrotic core, and inflammatory cells. Results Surgery mice showed a pronounced elevation of serum amyloid A (SAA) and developed increased plaque and necrotic core area already at 5 days, which reached significance at 15 days (p = 0.019; p = 0.004 for plaque and necrotic core, respectively). Macrophage and lymphocyte density significantly decreased in the surgery group compared to the control group at 15 days (p = 0.037; p = 0.024, respectively). The density of neutrophils and mast cells remained unchanged. Conclusions Major orthopedic surgery in ApoE−/− mice triggers a systemic inflammatory response. Atherosclerotic plaque area is enlarged after surgery mainly due to an increase of the necrotic core. The role of intra-plaque inflammation in this response to surgical injury remains to be fully elucidated. © 2016 Elsevier Ireland Ltd

Life
MHR - Metabolic Health Research
ELSS - Earth, Life and Social Sciences
Biomedical Innovation
Biology
Healthy Living
Animal model
Atherosclerosis
Inflammation
Myocardial infarction
Surgery

http://resolver.tudelft.nl/uuid:c805ef8c-07ea-4bdd-b077-f36c6dfb2deb

https://doi.org/10.1016/j.atherosclerosis.2016.07.909

575108

0021-9150

Atherosclerosis, 255, 164-170

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