Tj. Resink et al., LOW- AND HIGH-DENSITY-LIPOPROTEINS AS MITOGENIC FACTORS FOR VASCULAR SMOOTH-MUSCLE CELLS - INDIVIDUAL, ADDITIVE AND SYNERGISTIC EFFECTS, Journal of vascular research, 32(5), 1995, pp. 328-338
The mitogenic activities of low (LDL)- and high (HDL)-density lipoprot
eins have been examined in cultures of human vascular smooth muscle ce
lls (VSMC). LDL and HDL(3) dose-dependently (EC(50) values similar to
50 mu g/ml) stimulated DNA and protein synthesis ([H-3]-thymidine and
[H-3]-leucine incorporation, respectively) in the absence of exogenous
ly added mitogens. The synthetic responses of VSMC to combinations of
LDL and HDL(3) were additive, indicating that each lipoprotein mediate
s discrete effects. LDL or HDL(3) promoted VSMC proliferation under st
rict mitogen-free conditions, but this growth response was not sustain
ed. VSMC exposed to combinations of lipoproteins (either LDL or HDL(3)
) and growth factors (either PDGF-BB, EGF, bFGF or IGF) exhibited syne
rgistic DNA synthesis responses. In the combined presence of PDGF-BB a
nd either LDL or HDL(3), VSMC proliferation was sustained. Anionized l
ipoprotein preparations (oxidized, acetylated, carbamylated or malonim
ylated) also stimulated DNA and protein synthesis. Since the antioxida
nt beta-hydroxylated toluene did not block the effect of native LDL on
DNA synthesis, and fucoidin, a specific competitor for the 'scavenger
' receptor, did not inhibit. oxidized LDL-induced DNA synthesis, activ
ation of mitogenic signals by lipoproteins does not depend on lipid pe
roxidation. Rather, the apparent intrinsic mitogenic potential of lipo
proteins may depend upon their direct activation of replication-couple
d signal transduction systems.