O-Acylated heparin derivatives with low anticoagulant activity decrease proliferation and increase α-smooth muscle actin expression in cultured arterial smooth muscle cells

Abstract

Selectively O-acylated derivatives of various glycosaminoglycans were prepared and tested in vitro for their anticoagulant activity and their antiproliferative effect on rat and rabbit smooth muscle cells. When O-acylation (butyrylation or hexanoylation) had been performed on periodate-depolymerized heparin fragments having very low anticoagulant activity, the antiproliferative potency was markedly increased (IC 50 = 2 and 1 μg/ml respectively, versus 31 μg/ml for starting compound) without an increase in anticoagulant activity. The antiproliferative activity was related to the degree of acylation. The O-acylated derivatives of heparin fragments were also very active in reversing the de-differentiation of smooth muscle cell in culture, as estimated by the increase in the expression of α-smooth muscle actin and α-smooth muscle actin mRNA.