Remnant-like lipoprotein particles in type 2 diabetic patients with apolipoprotein E3/3 and apolipoprotein E2 genotypes.
Apolipoprotein (apo) E2 and diabetes mellitus are known to be associated with an accumulation of remnant lipoproteins in plasma. In this study, effects of type 2 diabetes mellitus and/or apo E2 genotypes on remnant-like lipoprotein particles (RLP) were assessed. Thirty-three subjects were divided into 6 groups: 7 apo E3/3 nondiabetic subjects, 6 apo E3/3 diabetic patients, 5 apo E3/2 nondiabetic subjects, 6 apo E3/2 diabetic patients, 5 apo E2/2 nondiabetic subjects, and 4 apo E2/2 diabetic patients. First, the effect of diabetes mellitus on RLP were estimated by comparing the apo E3/3 nondiabetic group with the apo E3/3 diabetic group. Plasma levels of RLP-cholesterol (chol) in the apo E3/3 diabetic group and the uptake of RLP from the apo E3/3 diabetic group by macrophages were significantly greater compared with the apo E3/3 nondiabetic group. Second, the effect of apo E2 on RLP was estimated in nondiabetic subjects. Apo E2/2 nondiabetic subjects had type III hyperlipoproteinemia (HLP). Plasma levels of RLP-chol in the apo E2/2 nondiabetic group and the uptake of RLP from the apo E2/2 nondiabetic group by macrophages were significantly greater compared with the apo E3/3 and apo E3/2 nondiabetic groups. Third, the effects of both apo E2 and diabetes on RLP were estimated. Plasma levels of RLP-chol in the apo E2 (E3/2 and E2/2) diabetic groups and the uptake of RLP from apo E2 (E3/2 and E2/2) diabetic groups by macrophages were significantly greater compared with apo E3/3 nondiabetic and diabetic groups or the apo E3/2 nondiabetic group. In diabetes, a gene dose effect of apo E2 on plasma levels of RLP-chol and uptake of RLP by macrophages was present (apo E3/3 < apo E3/2 < apo E2/2). The apo E2/2 diabetic group had type III HLP. Furthermore, uptake of RLP from the apo E2/2 diabetic group with type III HLP was significantly greater compared with the apo E2/2 nondiabetic group with type III HLP. In conclusion, type 2 diabetes was associated with increased RLP-chol in plasma and atherogenic RLP. In nondiabetes, apo E2/2 contributes to increased plasma RLP-chol and atherogenic RLP. In diabetes, additional effects of apo E2 to increase RLP-chol in plasma and to enhance the uptake of RLP by macrophages are present. RLP from apo E2/2 diabetes with type III HLP are more atherogenic than those from apo E2/2 nondiabetes with type III HLP.
Saito
Mieko
M
Department of Medicine, Diabetes and Endocrine Division, Kawasaki Medical School, Kurashiki, Japan.
Eto
Masaaki
M
Kaku
Kohei
K
D000328:Adult; D000368:Aged; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000209:etiology; D002784:Cholesterol / Q000097:blood* / Q000502:physiology; D002788:Cholesterol Esters / Q000096:biosynthesis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D005260:Female; D005838:Genotype; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood* / Q000502:physiology
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008074:Lipoproteins; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D002784:Cholesterol