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A model of neointima formation in the atherosclerotic carotid artery of mice

^a Crafoord Laboratory of Experiment Surgery, Karolinska Hospital, 17176 Stockholm, Sweden
^b Department of Thoracic Surgery, Karolinska Hospital, 17176 Stockholm, Sweden

^* Corresponding author. Tel.: +46-8-517-74846; fax: +46-8-517-73557
guro.valen{at}cmm.ki.se

To establish a simple, reproducible model of neointima formation in mice with atherosclerotic vessels. Apolipoprotein E/low density lipoprotein receptor double knockout mice were fed an atherogenic diet. Carotid artery injury was induced by separate ligation of the external and internal carotid artery immediately distal to the bifurcation. Mice with normal vessels were used for comparison. Monocytes and macrophages were detected with immunohistochemistry using CD68 antibodies. The transcription factor nuclear factor kappa B was also detected by immunohistochemistry. Expression of tumor necrosis factor- (TNF-) and interleukin-1ß (IL-1ß) was evaluated by real time polymerase chain reaction. Neointima and media areas were digitally measured and analyzed. Four weeks later carotid artery ligation had induced neointima formation proximal to the ligation site, apparent as a smooth muscle cell alpha-actin positive layer intimal to the lamina elastica interna. The shape and size of the lesions were reproducible. Nuclear localization of nuclear factor kappa B was found, and the expression of TNF- and IL-1ß increased after injury. CD68 positive cells were detected in the lumen, in the media and in the neointima. We have established in atherosclerotic mice a reproducible model of arterial injury with inflammation and neointima formation.

Key Words: Neointimal formation; Arterial injury; Apolipoprotein E; Inflammation; Nuclear factor kappa B