Differential metabolism of human VLDL according to content of ApoE and ApoC-III

We studied the metabolism of very low density lipoprotein (VLDL) and interm ediate density lipoprotein (IDL) particles that did or did not have apolipo protein 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 u ltracentrifuged 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-I II (apoC-III) content than did the corresponding E-particles. Most light VL DL apoE+ underwent lipolysis to dense VLDL E+ with reduced apoC-III content , which was removed from the circulation without conversion to IDL. In cont rast, most light VLDL apoE-, poor in apoC-III, was removed from the circula tion, and a smaller proportion underwent lipolysis to dense VLDL E-. Most d ense 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 con clusion, metabolism of human VLDL particles is influenced by their content of apoE, further modulated by the coexistence of apoC-III.