title: Insolubilization of low density lipoprotein induces cholesterol accumulation in cultured subendothelial cells of human aorta.
abstract: Primary cultures of typical and modified smooth muscle cells isolated from the intima of human aorta were used to study the mechanism whereby low density lipoprotein (LDL) induces accumulation of intracellular cholesterol. Incubation of intimal cells with native LDL obtained from human plasma did not lead to deposition of total cholesterol. LDL added to the cultures simultaneously with hyaluronic acid, heparin, chondroitin sulfate, fibronectin, and mouse monoclonal antibody against LDL also failed to alter the cellular cholesterol. On the other hand, 24-h incubation of the cells with LDL in the presence of dextran sulfate, gelatin, particles of aortic elastin, particles of collagenase-resistant aortic matrix, goat polyclonal antibodies against LDL or latex beads caused a significant (1.5-7-fold) increase in total cholesterol. The compounds which stimulated cholesterol deposition are able to form precipitating complexes with LDL. On the contrary, the agents which failed to induce cholesterol accumulation were unable to insolubilize LDL. A direct correlation (r = 0.927) was found between the cholesterol content of the insoluble complex and the increment of cholesterol in the cultured cells. To find out whether LDL plays a specific role in the deposition of intracellular cholesterol, very low density lipoproteins and high density lipoproteins were used. These lipoproteins stimulated the accumulation of intracellular cholesterol in the presence of agents capable of forming insoluble associates with them. Our data suggest that insolubilization of lipoproteins is a key event in the LDL-mediated accumulation of intracellular cholesterol induced by various agents.
authors: Institute of Experimental Cardiology, Cardiology Research Center of the U.S.S.R., Academy of Medical Sciences, Moscow.
authors: A N
authors: AN
authors: Orekhov
authors: V V
authors: VV
authors: Tertov
authors: D N
authors: DN
authors: Mukhin
authors: V E
authors: VE
authors: Koteliansky
authors: M A
authors: MA
authors: Glukhova
authors: M G
authors: MG
authors: Frid
authors: G K
authors: GK
authors: Sukhova
authors: K A
authors: KA
authors: Khashimov
authors: V N
authors: VN
authors: Smirnov
mesh_terms: D001018:Aortic Diseases / Q000209:etiology*; D001344:Autopsy; D008076:Cholesterol, HDL / Q000032:analysis*; D008078:Cholesterol, LDL / Q000032:analysis* / Q000276:immunology; D004730:Endothelium, Vascular; D005353:Fibronectins / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000032:analysis* / Q000276:immunology; D008079:Lipoproteins, VLDL / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D012995:Solubility
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005353:Fibronectins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D006493:Heparin