Expression of apolipoprotein E by cultured vascular smooth muscle cells is controlled by growth state.
Rat vascular smooth muscle cells (SMC) in culture synthesize and secrete a approximately 38,000-Mr protein doublet or triplet that, as previously described (Majack and Bornstein. 1984. J. Cell Biol. 99:1688-1695), rapidly and reversibly accumulates in the SMC culture medium upon addition of heparin. In the present study, we show that this approximately 38,000-Mr heparin-regulated protein is electrophoretically and immunologically identical to apolipoprotein E (apo-E), a major plasma apolipoprotein involved in cholesterol transport. In addition, we show that expression of apo-E by cultured SMC varies according to growth state: while proliferating SMC produced little apo-E and expressed low levels of apo-E mRNA, quiescent SMC produced significantly more apo-E (relative to other proteins) and expressed markedly increased levels of apo-E mRNA. Northern analysis of RNA extracted from aortic tissue revealed that fully differentiated, quiescent SMC contain significant quantities of apo-E mRNA. These data establish aortic SMC as a vascular source for apo-E and suggest new functional roles for this apolipoprotein, possibly unrelated to traditional concepts of lipid metabolism.
Majack
R A
RA
Atherosclerosis and Thrombosis Research, Upjohn Company, Kalamazoo, Michigan 49001.
Castle
C K
CK
Goodman
L V
LV
Weisgraber
K H
KH
Mahley
R W
RW
Shooter
E M
EM
Gebicke-Haerter
P J
PJ
D000818:Animals; D001011:Aorta; D001057:Apolipoproteins E / Q000096:biosynthesis* / Q000235:genetics; D002455:Cell Division; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D011233:Precipitin Tests; D012313:RNA / Q000032:analysis; D051381:Rats
D001057:Apolipoproteins E; D012313:RNA