Modification of low density lipoprotein by desialylation causes lipid accumulation in cultured cells: discovery of desialylated lipoprotein with altered cellular metabolism in the blood of atherosclerotic patients.
Low density lipoprotein (LDL) isolated from the blood of healthy donors was partially desialylated by incubating the lipoprotein with sialidase (neuraminidase). The addition of LDL treated with neuraminidase to cultured human aortic intimal cells of smooth muscle origin caused a substantial increase in intracellular cholesteryl esters, free cholesterol and triglycerides. Cultured cells took up and degraded desialylated LDL much more effectively than untreated (native) LDL. LDL were also isolated from an atherogenic blood plasma of patients with coronary artery disease, i.e. the plasma capable of inducing the accumulation of lipids in cultured cells. Patients' LDL, similarly to the mother plasma, were atherogenic, i.e. stimulated the accumulation of intracellular lipids. LDL isolated from nonatherogenic plasma of healthy donors proved to be nonatherogenic. Atherogenic patients' LDL had a 2- to 5-fold lower level of sialic acid as compared with nonatherogenic LDL of healthy donors. The uptake and degradation of atherogenic patients' LDL were much more effective than in the case of nonatherogenic LDL of healthy donors. We assume that atherogenic properties of LDL obtained from patients' blood plasma are explained exactly by a low sialic acid content.
Orekhov
A N
AN
Institute of Experimental Cardiology, USSR Cardiology Research Center, Moscow, Russia.
Tertov
V V
VV
Mukhin
D N
DN
Mikhailenko
I A
IA
D000328:Adult; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase; D012794:Sialic Acids / Q000097:blood; D014280:Triglycerides / Q000378:metabolism
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D012794:Sialic Acids; D014280:Triglycerides; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid