PROMOTION OF AORTIC SMOOTH-MUSCLE CELL-PROLIFERATION BY HYPERCHOLESTEROLEMIC LDL AND ITS SUPPRESSION BY HEPARIN OR SULFATED GLYCOSAMINOGLYCANS

Citation
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
Citations number
57
Categorie Soggetti
Biology,"Cytology & Histology
ISSN journal
10158987
Volume
4
Issue
1-2
Year of publication
1994
Pages
57 - 71
Database
ISI
SICI code
1015-8987(1994)4:1-2<57:POASCB>2.0.ZU;2-N
Abstract
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.