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 artery smooth muscle cell proliferation in vitro and prevent hypoxic vascular remodeling in vivo. In an attempt to understand the structural determinants of heparin's antiproliferative properties, we have fractionated an antiproliferative preparation of commercial heparin into low and high molecular weight fractions. Then the high molecular weight heparin 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 fractions were assayed for antiproliferative effects on cultured bovine pulmonary artery smooth muscle cells. No appreciable differences were found among high and low molecular weight heparin fractions The core peptides showed no antiproliferative activity. However, higher charge density fraction was less antiproliferative. Copyright 1997 Academic Press.