THE DIFFERENTIAL DISTRIBUTION OF HYALURONIC-ACID IN THE LAYERS OF HUMAN ATHEROMATIC AORTAS IS ASSOCIATED WITH VASCULAR SMOOTH-MUSCLE CELL-PROLIFERATION AND MIGRATION

Vascular smooth muscle cells (VSMC), under conditions of induced proli feration, similar to those involved in atherosclerosis, secrete an aci dic glycan, 82% of which exhibits structural homology with hyaluronic acid (HA), has a molecular mass of 340 kDa (HA-340) and inhibits VSMC proliferation in vitro. In this study, the expression of glycans was i nvestigated in human atheromatic aortas and evidence is presented that a HA molecule, similar to HA-340, is distinctly expressed in all aort ic layers. The isolation of the glycans from human aortas was performe d after homogenization of the individual aortic layers (atheromatic pl aque, tunica intima, tunica media and tunica adventitia), by lipid ext raction and extensive digestion with pronase and DNase. The total glyc ans were purified from the digestion products by gel filtration on Sep hadex G-25 and fractionated on a Superose 6 column. Enzymatic treatmen t of the ensuing glycan fractions with all known glycosaminoglycan-deg rading enzymes, followed by electrophoresis on polyacrylamide gradient gels and cellulose acetate membranes, revealed that, in addition to H A, the tunica intima and the atheromatic plaque also contained dermata n sulfate, while the tunica media and the tunica adventitia also conta ined chondroitin sulfates and heparan sulfate. The highest concentrati on of the human aorta HA was found in the tunica media, exhibiting a n egative concentration gradient from the tunica media to the atheromati c plaque. Investigation of the biological function of the human aorta HA revealed that this molecule acts as a negative regulator on the PDG F-induced VSMC proliferation and as a positive regulator on the PDGF-i nduced VSMC migration. The differential expression of HA within the ao rtic layers correlates with the biological function attributed to this acidic glycan and associates it with key events in the progression of atherogenesis. (C) 1998 Elsevier Science Ireland Ltd. All rights rese rved.