Non-invasive means to study the functional status of sinusoidal liver endothelial cells

Circulating connective tissue macromolecules are efficiently eliminated by receptor-mediated endocytosis in liver endothelial cells (LEC). In patients with a seriously diseased liver, for example in liver cirrhosis or when a transplanted liver is about to be rejected, dysfunctional LEC or altered blood perfusion through the liver results in significantly increased serum levels of connective tissue macromolecules and other substances that are normally taken up by LEC. With the aid of high affinity antibodies or other kinds of binding proteins it has been possible to measure a number of connective tissue macromolecules in the blood, and some of these substances have been used to diagnose serious liver disease. However, the metabolic patterns of these molecules are such that it is difficult to extrapolate directly on the basis of increased serum levels to conclude that the main underlying cause of increased serum levels is dysfunctional LEC. Elevated serum levels of many connective tissue proteins may reflect either increased synthesis, increased release from cell or tissue depots, and/or decreased removal by LEC. Therefore, to use measurement of serum connective tissue molecule levels as indicators of LEC function, it is imperative to know the catabolic routes of these substances in health and disease. Due to the fact that we presently know more about the total metabolic pattern of hyaluronan (HYA) than of other connective tissue macromolecules that are cleared solely by LEC, serum HYA should be preferentially used to monitor the function of LEC, in particular in liver transplantation and cirrhosis.