SELECTIVE RETENTION OF VLDL, IDL, AND LDL IN THE ARTERIAL INTIMA OF GENETICALLY HYPERLIPIDEMIC RABBITS IN-VIVO - MOLECULAR-SIZE AS A DETERMINANT OF FRACTIONAL LOSS FROM THE INTIMA INNER MEDIA

To explore possible mechanisms whereby the triglyceride-rich lipoprote ins IDL and VLDL may promote atherosclerosis, fractional loss of these lipoproteins from the intima-inner media was measured in vivo in gene tically hyper lipidemic rabbits of the St Thomas's Hospital strain and compared with the fractional loss of LDL, HDL, and albumin. These rab bits exhibit elevated plasma levels of VLDL, IDL, and LDL. In each rab bit, two aliquots of the same macromolecule, one iodinated with I-125 and the other with I-131, respectively, were injected intravenously on average 24 and 3 hours, respectively, before removal of the aortic in tima-inner media. The fractional loss from the intima-inner media of n ewly entered macromolecules was then calculated. The average fractiona l losses for VLDL, IDL, LDL, HDL, and albumin in lesioned aortic arche s were 0.1%/h (n=4), -0.2%/h (n=3), 1.8%/h (n=4), 11.4%/h (n=3), and 2 6.3%/h (n=1), respec tively; in nonlesioned aortic arches fractional l osses for IDL, LDL, HDL, and albumin were 1.7%/h (n=1), 0.6%/h (n=2), 14.6%/h (n=3), and 25.9%/h (n=3). In both lesioned and nonlesioned aor tic arches, the logarithms of these fractional loss values were invers ely and linearly dependent on the diameter of the macromolecules (R(2) =.57, P=.001 and R(2)=.84, P<.001), as determined from electron photom icrographs of negatively stained lipoproteins. These results suggest t hat after uptake into the arterial intima, VLDL and IDL as well as LDL are selectively retained in comparison with HDL and albumin.