H. Tasaki et al., PROMOTION OF AORTIC SMOOTH-MUSCLE CELL-PROLIFERATION BY HYPERCHOLESTEROLEMIC LDL AND ITS SUPPRESSION BY HEPARIN OR SULFATED GLYCOSAMINOGLYCANS, Cellular physiology and biochemistry, 4(1-2), 1994, pp. 57-71
The effects of low-density lipoprotein (LDL) from normolipidemic (NL)
and familial hypercholesterolemic (FH) human subjects on the smooth mu
scle cell (SMC) proliferation were examined, along with the antiprolif
erative actions of heparin and glycosaminoglycans (GAGs) in this syste
m. Cell growth was stimulated from 146 to 176% by FH- over NL-LDL. Thi
s proliferative effect of FH-LDL was accompanied by an increase in the
membrane cholesterol content and an increase in Ca2+ influx. These ef
fects of FH-LDL were partially inhibited (50%) following methylation o
f apoprotein B100. The effects of FH-LDL were abolished by heparin and
sulfated GAGs and this inhibitory effect was also accompanied by norm
alization of Ca2+ influx and cell membrane cholesterol. Electrokinetic
analysis demonstrated a reduced net negative charge of FH-LDL relativ
e to that of NL-LDL. We hypothesize that LDL surface charge may regula
te the movement of cholesterol into the SMC plasma membrane where its
presence in excess alters SMC function. Taken together, these results
implicate a role for FH-LDL cholesterol as an important factor in the
alteration of SMC cell growth kinetics in hypercholesterolemia, a proc
ess which can be modulated by heparin and sulfated GAGs.