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(Stroke. 2006;37:2625.)
© 2006 American Heart Association, Inc.

Original Contributions

Increased Balloon-Induced Inflammation, Proliferation, and Neointima Formation in Apolipoprotein E (ApoE) Knockout Mice

Christian M. Matter, MD; Liming Ma, MD; Tobias von Lukowicz, MD; Patricia Meier; Christine Lohmann; Dongming Zhang, MD; Ülkan Kilic, PhD; Eugen Hofmann; Suk-Woo Ha, PhD; Martin Hersberger, PhD; Dirk M. Hermann, MD Thomas F. Lüscher, MD

From the Cardiovascular Research (C.M.M., L.M., T.v.L., P.M., C.L., D.Z., T.F.L.), Institute of Physiology, Zurich University and Cardiology, CardioVascular Center, University Hospital Zurich; the Center for Integrative Human Physiology (C.M.M., T.v.L., P.M., C.L., Ü.K., M.H., D.M.H., T.F.L.), Zurich University; the Department of Neurology (Ü.K., D.M.H.), University Hospital Zurich; Schneider Europe (E.H.), Bulach; Jomed (S.-W.H.), Beringen; Institute of Clinical Chemistry (M.H.), University Hospital Zurich, Switzerland.

Correspondence to Christian M. Matter, MD, Cardiovascular Research, Institute of Physiology, Zurich University and Cardiology CardioVascular Center, University Hospital Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. E-mail cmatter{at}physiol.unizh.ch

Background and Purpose— The pathophysiology of vascular lesions after balloon angioplasty remains poorly understood. A major limitation of most experimental studies in this regard is that injury was assessed in healthy arteries. Our aim was to study the effects of hypercholesterolemia in a mouse vascular injury model that mimics human balloon angioplasty.

Methods— Carotid balloon distension was performed in wild-type (WT) mice on a normal diet (ND), in apolipoprotein E–deficient (ApoE^–/–) mice on ND and in ApoE^–/– mice fed a high cholesterol diet (CD).

Results— Medial cell death (TUNEL) was elevated in all mice at 1 hour and 1 day after angioplasty without differences between the groups. We found enhanced intimal inflammation (%CD45-positive cells) and vascular cell adhesion molecule-1 expression at 7 days (P<0.05; n4) as well as increased proliferation rates (BrdU-index) in ApoE^–/– CD at 7 and 28 days postinjury (P<0.05; n5). Four weeks after injury, these events led to enhanced neointima in ApoE^–/– CD compared with WT ND mice (intima/media, P<0.001; n8). The amount of lesion formation paralleled the incremental increase in total plasma cholesterol in WT ND, ApoE^–/– ND and ApoE^–/– CD (P<0.01).

Conclusions— Carotid balloon distension injury in ApoE^–/– mice on CD induced enhanced inflammation and proliferation leading to increased neointima. Further applications of this microballoon catheter in genetically modified mice will provide opportunities to elucidate molecular mechanisms of vascular lesion formation in a model that reflects clinical balloon angioplasty. This know-how may pave the way to catheter-based interventions of human microvessels in the peripheral or cerebral circulation.

Key Words: cholesterol • angioplasty • inflammation • apolipoprotein E