Remnant-like very-low-density lipoprotein isolated from hypertriglyceridemic patients by immunoaffinity chromatography suppressed 3-hydroxy-3-methylglutaryl coenzyme A activity of cultured human skin fibroblasts.
It has been previously reported that VLDL unbound to monoclonal antibody against apoB-100 was rich in apoE, thus resembling remnant particles (J Lipid Res, 1993:33;369-380). In the current study, we have further analyzed the unbound VLDL fraction in plasma from hypertriglyceridemic patients using a mixture of monoclonal antibodies against apoB-100 and apoA-1. The unbound VLDL isolated from the plasma of hypertriglyceridemic patients was found to be rich in apoE, apoB-48, and triglyceride compared with the bound VLDL. Furthermore, these unbound VLDL, but not bound VLDL, significantly suppressed HMG CoA reductase activity of cultured human skin fibroblasts (-20 to -25%, P = 0.0022). The degree of suppression is significantly correlated with the apoE content of unbound VLDL (r = -0.769, P < 0.05). Unbound VLDL failed to suppress the activity of HMG CoA reductase of LDL receptor negative fibroblasts. These observations indicate a potential atherogenicity of remnant-like unbound VLDL by delivering more cholesterol through the LDL receptor dependent pathway with apoE as a ligand. In conclusion, this new immunoaffinity chromatography system is a useful method for directly quantifying atherogenic remnants in plasma.
Shige
H
H
First Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Ishikawa
T
T
Ikewaki
K
K
Nishiwaki
M
M
Higashi
K
K
Nakajima
K
K
Nakamura
H
H
D000328:Adult; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000494:pharmacology; D001057:Apolipoproteins E / Q000302:isolation & purification* / Q000494:pharmacology; D002846:Chromatography, Affinity; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D015228:Hypertriglyceridemia / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood / Q000302:isolation & purification* / Q000494:pharmacology*; D008297:Male; D014280:Triglycerides / Q000494:pharmacology
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D006903:Hydroxymethylglutaryl CoA Reductases; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent