Compartmentalization of water in human atherosclerotic lesions. Changes in distribution and exclusion volumes for plasma macromolecules.

Abstract

High concentrations of LDL and other plasma macromolecules are present in normal aortic intima and early proliferative atherosclerotic lesions that have not yet accumulated lipid. Their compartmentalization within the tissue water was estimated from the concentrations of low density lipoprotein (LDL), alpha 2-macroglobulin (alpha 2-M), and albumin in interstitial fluid and adjacent intimal tissue. Interstitial fluid was collected on filter paper inserted into natural strip planes in the intima; macromolecules in interstitial fluid and tissue were assayed by rocket immunoelectrophoresis directly from the papers or tissue. From their concentrations in interstitial fluid and total tissue water, the fractional and absolute volumes in which they were distributed (distribution volume) or from which they were excluded (exclusion volume) were calculated for each macromolecule. Compared with normal intima, the distribution volume increased by 60% and the exclusion volume by 95% in early gelatinous lesions; exclusion volume fraction was linearly related to molecular mass. In more advanced lesions, there was disproportionate exclusion of LDL and alpha 2-M. Their distribution volumes decreased and their concentrations in interstitial fluid increased; the concentration showed a significant inverse relation with distribution volume (regression coefficient, b = -0.53, p less than 0.01). Redistribution of tissue water may concentrate LDL in interstitial fluid, and contribute to its extracellular deposition.