Increased balloon-induced inflammation, proliferation, and neointima formation in apolipoprotein E (ApoE) knockout mice.
OBJECTIVE
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; n > or = 4) as well as increased proliferation rates (BrdU-index) in ApoE-/- CD at 7 and 28 days postinjury (P < 0.05; n > or = 5). Four weeks after injury, these events led to enhanced neointima in ApoE-/- CD compared with WT ND mice (intima/media, P < 0.001; n > or = 8). 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.
Matter
Christian M
CM
Cardiovascular Research, Institute of Physiology, Zurich University and Cardiology CardioVascular Center, University Hospital Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. cmatter@physiol.unizh.ch
Ma
Liming
L
von Lukowicz
Tobias
T
Meier
Patricia
P
Lohmann
Christine
C
Zhang
Dongming
D
Kilic
Ulkan
U
Hofmann
Eugen
E
Ha
Suk-Woo
SW
Hersberger
Martin
M
Hermann
Dirk M
DM
Lüscher
Thomas F
TF
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D017209:Apoptosis; D020212:Carotid Artery Injuries / Q000209:etiology* / Q000473:pathology; D002455:Cell Division; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000473:pathology; D006937:Hypercholesterolemia / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D006965:Hyperplasia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D015539:Platelet Activation; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis; D014657:Vasculitis / Q000209:etiology* / Q000473:pathology
D001057:Apolipoproteins E; D019010:Vascular Cell Adhesion Molecule-1