ApoE genotype-specific inhibition of apoptosis.
Endothelial cell apoptosis can be initiated by withdrawing growth factors or serum, and is inhibited by HDL. Our results show that the total lipoprotein population from apolipoprotein E 4/4 (APOE4/4) sera is less anti-apoptotic than total lipoproteins from other APOE genotypes, as measured by caspase 3/7 activity. Moreover, APOE4/4 VLDL antagonizes the antiapoptotic activity of HDL by a mechanism requiring binding of apoE4 on VLDL particles to an LDL family receptor. This ability of APOE4/4 VLDL to inhibit the antiapoptotic effects of HDL presents a potential mechanism by which the expression of several diseases, including atherosclerosis, is enhanced by the APOE4 genotype.
DeKroon
Robert M
RM
Division of Neurology, Duke University Medical Center, Durham, NC 27710, USA.
Mihovilovic
Mirta
M
Goodger
Zoe V
ZV
Robinette
Jennifer B
JB
Sullivan
Patrick M
PM
Saunders
Ann M
AM
Strittmatter
Warren J
WJ
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D008076:Cholesterol, HDL / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008246:Lysophospholipids / Q000097:blood
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008079:Lipoproteins, VLDL; D008246:Lysophospholipids; D020169:Caspases