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. METHODS AND 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.
OBJECTIVE:Apolipoprotein E (apoE) reduces mouseatherosclerosis progression independent of plasma cholesterol level effects. A mouseartery injury model was used to examine whether apoE exhibits beneficial lipid-independent effects on neointimal formation. METHODS AND 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.
Authors: Paul A Mueller; Lin Zhu; Hagai Tavori; Katherine Huynh; Ilaria Giunzioni; John M Stafford; MacRae F Linton; Sergio Fazio Journal: Circulation Date: 2018-10-23 Impact factor: 29.690
Authors: Amanda L Brown; Xuewei Zhu; Shunxing Rong; Swapnil Shewale; Jeongmin Seo; Elena Boudyguina; Abraham K Gebre; Martha A Alexander-Miller; John S Parks Journal: Arterioscler Thromb Vasc Biol Date: 2012-07-19 Impact factor: 8.311
Authors: Zhi H Huang; Catherine A Reardon; Papasani V Subbaiah; Godfrey S Getz; Theodore Mazzone Journal: J Lipid Res Date: 2012-10-15 Impact factor: 5.922