Structural Determinants of the Antiproliferative Effect of Heparin Molecule on Human Mesangial Cell

ABSTRACTAIMTo determine the structural determinants of the antiproliferative effect of heparin molecules on human mesangial cell.METHODSUnfractionated heparin was separately desulfated, periodate-oxidized/borohydride-reduced, carboxyl-reduced and poly-sulfated by chemical modification. These heparin derivates were assayed for antiproliferative effects on cultured human mesangial cell compared with unfractionated heparin.RESULTS and CONCLUSION2, 3-O-desulfated heparin almost completely lost the antiproliferative activity at concentration between 0.01∼1.5 mg·mL−1, 6-O-desulfated, N-desulfated and carboxyl reduced heparin significantly lost some activities compared with heparin, but periodate-oxidized/borohydride-reduced, poly-sulfated heparin and enoxaparin exhibited comparable growth-inhibition effects on human mesangial cell. The anticoagulation activity of heparin derivates markedly decreased by APTT. These data suggest that 2-O- or 3-O-sulfation is much more important than 6-O- and N-sulfation to antiproliferative activity. Sulfate and carboxyl are factors but not essential reasons. Antiproliferative effect is also independent on heparin polysaccharide chain, anticoagulation activity and molecular size exceeding 4.5 kDa.