LIPOPROTEINS AND THE LIVER SIEVE - THE ROLE OF THE FENESTRATED SINUSOIDAL ENDOTHELIUM IN LIPOPROTEIN METABOLISM, ATHEROSCLEROSIS, AND CIRRHOSIS

The liver sieve, formed by the fenestrated hepatic sinusoidal endothel ium, is a dynamic biofilter separating the hepatic blood from the plas ma within the space of Disse. It filters macromolecules of differing s izes, especially lipoproteins. More specifically, it acts as a barrier to the large triglyceride-rich parent chylomicrons, while permitting the smaller triglyceride-depleted but cholesterol- and retinol-rich re mnants to enter the space of Disse. There the remnants contact specifi c receptor sites on the hepatocyte microvilli, Thus, the liver sieve i s the first site of hepatic selection and consequent metabolism of die tary cholesterol and fat-soluble vitamins, as well as rejection of die tary triglycerides. Therefore, perturbations of the porosity of the si eve, whether from changes in size, number of fenestrae, or composition of the underlying extracellular matrix within the space of Disse, wil l have profound influence on the metabolism of lipoproteins, This dist urbance of the homeostasis of lipids, including fat-soluble vitamins a nd cholesterol, as well as other macromolecules, may tilt the balance beta een health and disease in a variety of organs and tissues, such a s the liver, kidney and arteries.