INFLUENCE OF MOLECULAR-WEIGHT, PROTEIN CORE AND CHARGE OF NATIVE HEPARIN FRACTIONS ON PULMONARY-ARTERY SMOOTH-MUSCLE CELL-PROLIFERATION

Heparin macromolecules have been shown to inhibit cultured pulmonary a rtery smooth muscle cell proliferation in vitro and prevent hypoxic va scular remodeling in vivo. In an attempt to understand the structural determinants of heparin's antiproliferative properties, we have fracti onated an antiproliferative preparation of commercial heparin into low and high molecular weight fractions. Then the high molecular weight h eparin fraction was further fractionated on a DEAE-cellulose column by charge density eluting with 0 - 1 M NaCl linear gradient. The heparin protein peptides were both removed and isolated. These heparin fracti ons were assayed for antiproliferative effects on cultured bovine pulm onary artery smooth muscle cells. No appreciable differences were foun d among high and low molecular weight heparin fractions. The core pept ides showed no antiproliferative activity. However, higher charge dens ity fraction was less antiproliferative. (C) 1997 Academic Press.