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research
Orthopedic surgery increases atherosclerotic lesions and necrotic core area in ApoE-/- mice
Authors
Chen
Cohen
+38 more
Corrales-Medina
Dutta
Dutta
Gualandro
Hans W.M. Niessen
Hanson
Ilse P.A. Zethof
Janssen
Kaynar
King
Kleemann
Lalmohamed
Landesberg
Lars F.H. Theyse
Libby
Martine C. Morrison
Moore
Morrison
Naghavi
Paul A.J. Krijnen
Reid
Rianne van der Linden
Robert Kleemann
Santos-Gallego
Santos-Gallego
Santos-Gallego
Seimon
Smeeth
Tan
Thompson
Thompson
Van der Donckt
van Dijk
Virmani
Virmani
Wessel W. Fuijkschot
Yvo M. Smulders
Zhang
Publication date
1 January 2016
Publisher
'Elsevier BV'
Doi
Cite
Abstract
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 Lt
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info:doi/10.1016%2Fj.atheroscl...
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