Variability of the electrophoretic mobility of low density lipoprotein. Comparison of interstitial fluid from human aortic intima and serum.

Interstitial fluid was collected from human aortic intima and the low density lipoprotein (LDL) was compared with serum LDL by two-dimensional immunoelectrophoresis. In half the samples derived from normal intima the migration rate was within +/- 10% of migration of LDL in serum, but in the remaining samples it was higher, indicating an increase in net negative charge on the molecule. By contrast, in most samples of interstitial fluid from gelatinous thickenings the migration rate of LDL was lower than in serum, indicating reduction in net negative charge. To test for the effect of different electrolyte concentrations in interstitial fluid and serum, migration of alpha 2-macroglobulin (alpha 2-M) was measured simultaneously in both. This showed no significant difference between interstitial fluid and serum, and varied by less than 2% between different serum samples. However, the mobility of LDL relative to alpha 2-M showed a remarkable variation, ranging from 80.9 to 127.1% of alpha 2-M mobility in interstitial fluid and from 58.6 to 115.9% in 23 serum samples. In serum, LDL relative mobility showed no correlation with general acid-base status, as indicated by serum bicarbonate levels, with fatty meals or diabetic keto-acidosis, or with extent of glycosylation of haemoglobin. This suggested that the variation in surface charge is intrinsic to the molecule and not a transient reflection of the plasma environment. Experimental alterations in the surface charge of LDL change its interaction with smooth muscle cells and macrophages in vitro, and its mitogenic properties. This raises the possibility that physiological variation in the surface charge of LDL in different subjects could alter its atherogenic potential.