Three types of naturally occurring modified lipoproteins induce intracellular lipid accumulation in human aortic intimal cells--the role of lipoprotein aggregation.
Blood monocytes or intimal smooth muscle cells from normal aorta were incubated with low density lipoprotein (LDL) from patients with coronary atherosclerosis, or with LDL from diabetic patients, or with lipoprotein(a) (Lp(a)). In each case there was a 2- to 4-fold rise in the intracellular cholesteryl ester content. LDL from healthy subjects failed to induce intracellular lipid accumulation in these cells. LDL from patients with coronary atherosclerosis, LDL from diabetic patients, and Lp(a) form aggregates under cell culture conditions. The ability of these lipoproteins to increase the cholesteryl ester content of cultured cells is directly correlated to the degree of lipoprotein aggregation. When aggregates were removed from the lipoprotein preparations by filtration, the latter became less effective in promoting intracellular lipid accumulation. Incubation of cells with lipoprotein aggregates, isolated by gel filtration, induced a 3- to 5-fold elevation of the cellular cholesteryl ester content. These results suggest that LDL from atherosclerotic patients, or LDL from diabetic patients, or Lp(a) have a tendency to form aggregates and that these aggregates are avidly taken up by intimal smooth muscle cells followed by lipid accumulation. This aggregation tendency may play a role in atherogenesis.
Tertov
V V
VV
Institute of Experimental Cardiology, USSR Cardiology Research Center, Moscow.
Sobenin
I A
IA
Gabbasov
Z A
ZA
Popov
E G
EG
Yaroslavov
A A
AA
Jauhiainen
M
M
Ehnholm
C
C
Smirnov
V N
VN
Orekhov
A N
AN
D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010316:Particle Size
D002788:Cholesterol Esters; D017270:Lipoprotein(a); D008074:Lipoproteins; D008077:Lipoproteins, LDL