Subphysiologic apolipoprotein E (ApoE) plasma levels inhibit neointimal formation after arterial injury in ApoE-deficient mice.
OBJECTIVE
Apolipoprotein E (apoE) reduces mouse atherosclerosis progression independent of plasma cholesterol level effects. A mouse artery injury model was used to examine whether apoE exhibits beneficial lipid-independent effects on neointimal formation.


RESULTS
ApoE-deficient (apoE-/-), wild-type (WT), and transgenic apoE-/- mice (secreting apoE at different levels from adrenal glands) underwent femoral artery injury. Mice with low expression of plasma apoE (0.1% of WT) had cholesterol levels approximately half those of apoE-/- littermates (but still approximately 6x >WT). Mice with higher expression (HE; 2% to 3% of WT) of plasma apoE had cholesterol levels approximately twice those of WT. Injured WT mouse (versus apoE-/-) arteries had a smaller mean intima-to-media (I/M) ratio (0.87 versus 1.96; P<0.05). HE mice tended to have lower mean I/M ratios (1.3; P>0.05 versus apoE-/- mice). Multiple regression analysis indicated that apoE levels were significantly associated with reduced I/M ratios, but plasma cholesterol levels were not, before or after adjusting for apoE. In addition, foam cell content of the neointima and media of injured arteries, a negative prognostic indicator in postangioplasty human lesions, was inversely related to plasma apoE levels.


CONCLUSIONS
Similar to its effects on atherosclerosis progression, in a mouse model of restenosis, a subphysiological level of apoE was associated with beneficial effects on lesion size/composition.
Wientgen
Hilke
H
Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
Thorngate
Fayanne E
FE
Omerhodzic
Sabina
S
Rolnitzky
Linda
L
Fallon
John T
JT
Williams
David L
DL
Fisher
Edward A
EA
D000199:Actins / Q000032:analysis / Q000172:deficiency; D000818:Animals; D001057:Apolipoproteins E / Q000097:blood* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D002784:Cholesterol / Q000097:blood*; D005263:Femoral Artery / Q000293:injuries / Q000473:pathology*; D005487:Foam Cells / Q000473:pathology; D006965:Hyperplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017539:Tunica Intima / Q000473:pathology*
D000199:Actins; D001057:Apolipoproteins E; D002784:Cholesterol