Modified low density lipoprotein from diabetic patients causes cholesterol accumulation in human intimal aortic cells.
Fifty-five serum samples from 99 Type 1 and 71 serum samples from 81 Type 2 diabetic patients (56% and 88%, respectively) brought about a 1.5-3.5-fold increase in total cholesterol content of cultured human intimal aortic cells. This atherogenic effect did not correlate with patient's age, diabetes duration or plasma lipid levels, and was mainly due to low density lipoprotein (LDL). Cholesterol accumulation in cells incubated with LDL highly correlated with that in cells exposed to corresponding patient's serum (r = 0.872 and r = 0.811, P < 0.0001, in Type 1 and Type 2 diabetic patients, respectively). In LDL from diabetic patients the sialic acid content was decreased by an average of 30% (P < 0.05), as compared with healthy subjects, and the fructosyl lysine content was increased by an average of 25% (P < 0.05). Atherogenic effect of patients' LDL significantly correlated with their fructosyl lysine content (P < 0.0001) and negatively correlated with sialic acid content (P < 0.0001). Two LDL fractions were further separated from the total LDL preparation by affinity chromatography on Ricinus communis agglutinin-agarose. The bound (desialylated) LDL fraction was characterized by an increased fructosyl lysine content and the altered neutral lipid and phospholipid composition, while non-bound (sialylated) LDL fraction did not differ from normal LDL. Desialylated, but not sialylated, LDL fraction induced massive cholesterol accumulation in cultured cells. In conclusion, the cholesterol accumulating effect of diabetic patients' blood sera is mainly related to atherogenic low density lipoprotein fraction, which is modified in various ways--by increased non-enzymatic glycosylation, desialylation and alterations in lipid composition. This multiple-modified LDL may contribute to the premature atherosclerosis development in diabetes mellitus.
Sobenin
I A
IA
National Cardiology Research Center, Academy of Medical Sciences, Moscow, Russia.
Tertov
V V
VV
Koschinsky
T
T
Bünting
C E
CE
Slavina
E S
ES
Dedov
I I
II
Orekhov
A N
AN
D000293:Adolescent; D000328:Adult; D001011:Aorta / Q000378:metabolism*; D001161:Arteriosclerosis / Q000503:physiopathology; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000097:blood*; D005260:Female; D006801:Humans; D008055:Lipids / Q000032:analysis; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry / Q000502:physiology*; D008239:Lysine / Q000031:analogs & derivatives / Q000032:analysis; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid; D010743:Phospholipids / Q000032:analysis; D012794:Sialic Acids / Q000032:analysis; D017539:Tunica Intima / Q000378:metabolism*
D008055:Lipids; D008077:Lipoproteins, LDL; D010743:Phospholipids; D012794:Sialic Acids; C033186:fructosyl-lysine; D002784:Cholesterol; D019158:N-Acetylneuraminic Acid; D008239:Lysine