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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1494.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Differential Metabolism of Human VLDL According to Content of ApoE and ApoC-III

Koji Tomiyasu; Brian W. Walsh; Katsunori Ikewaki; Helena Judge; Frank M. Sacks

From the Department of Nutrition (K.T., K.I., H.J., F.M.S.), Harvard School of Public Health; the Department of Obstetrics and Gynecology (B.W.W.), Brigham and Women’s Hospital; and Channing Laboratory (F.M.S.), Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, Mass. Dr Tomiyasu is now at Tokorozawa City, Saitama, and Dr Ikewaki is now at Department of Cardiology, Jikei University School of Medicine, Tokyo, Japan.

Reprints requests to Frank M. Sacks, MD, Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115. E-mail fsacks{at}hsph.harvard.edu

Abstract—— We studied the metabolism of very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) particles that did or did not have apolipoprotein E (apoE) in 12 normolipidemic women by endogenously labeling plasma apolipoprotein B. The plasma was separated into bound (E+) and unbound (E-) fractions by use of a monoclonal antibody (1D7), and the fractions were ultracentrifuged to yield E+ and E- subfractions of light and dense VLDL and IDL. VLDL E+ and IDL E+ were produced mainly by the liver. VLDL E+ and IDL E+ had lower fractional catabolic rates and much higher apolipoprotein C-III (apoC-III) content than did the corresponding E- particles. Most light VLDL apoE+ underwent lipolysis to dense VLDL E+ with reduced apoC-III content, which was removed from the circulation without conversion to IDL. In contrast, most light VLDL apoE-, poor in apoC-III, was removed from the circulation, and a smaller proportion underwent lipolysis to dense VLDL E-. Most dense VLDL E- underwent lipolysis to IDL E-. The rate constant for lipolysis of dense VLDL to IDL was greater for E- than for E+, and the rate constant for clearance from plasma was greater for dense VLDL E+ than for E-. In conclusion, metabolism of human VLDL particles is influenced by their content of apoE, further modulated by the coexistence of apoC-III.

Key Words: lipoproteins • metabolism • apolipoprotein B • apolipoprotein E • apolipoprotein C-III

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