MINIMUM FRAGMENTS OF THE HEPARIN MOLECULE ABLE TO PRODUCE THE ACCUMULATION AND CHANGE OF THE SULFATION PATTERN OF AN ANTITHROMBOTIC HEPARAN-SULFATE FROM ENDOTHELIAL-CELLS

Heparin and low molecular weight heparins stimulate two to three fold the accumulation of an antithrombotic heparan sulfate secreted by endo thelial cells in culture. This led us to search for the minimum struct ural requirements of the heparin molecule able to elicit the enhanceme nt of the heparan sulfate. Fragments were prepared from heparin by deg radation with bacterial heparinase and heparitinases. A heparin pentas ulfated tetrasaccharide was shown to be the minimum structural sequenc e able to enhance two to three fold the secretion of heparan sulfate b y endothelial cells. The stimulation is specific for the endothelial c ell, is concentration dependent and the effect is already noticed afte r one hour of exposure of the cells to heparin and the tetrasaccharide . Degradation of the [S-35]-heparan sulfate synthesized in the presenc e of heparin or the tetrasaccharide has shown a higher degree of sulfa tion of its iduronic acid residues.