Intimal and medial plasma protein concentrations and endothelial function

Abstract

In normal human aortic intima the concentration of low density lipoprotein (LDL) was previously found to be about twice the concentration in the patient's plasma; by contrast, intimal albumin was only a quarter of the plasma concentration, and retention of other plasma proteins was a function of molecular weight. We have tried to elucidate some of the factors involved in this differential retention of proteins, and concentration of LDL, by further studies on early lesions and fibrin mural thrombi, with varying extent of endothelialization, in aortic samples from 35 subjects from whom blood was obtained within 2 days of death or reconstructive vascular surgery. In gelatinous lesions the concentration of LDL was more than twice the concentration in normal intima on a dry weight basis, but on the basis of wet weight there was little difference, and there was no change in the pattern of plasma protein distribution. This suggests that there is an increased “available space” for tissue fluid in the lesion, but no change in mechanism of uptake, or in specific sequestration. In non-endothelialized graft pseudo-intimas and fibrin mural thrombi LDL concentration was very low and the pattern of plasma proteins was the inverse of intima, with greater retention of albumin, high density lipoprotein (HDL) and α 2-macroglobulin than of LDL. With endothelialization of thrombi LDL concentration increased 5-fold, and the pattern of plasma proteins approached that of intima. Sheets of normal intima were stripped off the internal elastic lamina, divided into 2 equal parts, and one half immersed in the patient's own plasma. Compared with the control half, LDL decreased in all plasma equilibrated samples (mean 63%, P < 0.01) whereas albumin increased (mean 147%, P < 0.01). This supports the idea that LDL concentration in intima is greater than in plasma and, as it is freely diffusable, suggests that it is in free solution and not complexed with a component of the extracellular matrix. In gelatinous lesions most of the LDL was in a free fluid fraction that could be absorbed on filter paper. There was no uptake of LDL when sheets of normal media, with IEL removed, were equilibrated with plasma; proteins with molecular weight >10 6 Daltons appear to be excluded from the extracellular space of normal media. The results suggest that the endothelium is associated with the maintenance, against the concentration gradient, of a 2-fold increase in concentration of free LDL in intima compared with plasma, and possible mechanisms are discussed.