Anticoagulantly active heparin-like molecules from vascular tissue

Abstract

Mucopolysaccharides were isolated from calf cerebral microvasculature and calf aorta. The only complex carbohydrates that exhibited anticoagulant activity were heparin-like components. The biologic potencies of calf cerebral and aortic heparin-like species were 2.92 units/mg of anti-factor Xa activity and 2.85 units/mg of anti-factor IIa activity, as well as 0.56 unit/mg of anti-factor Xa activity and 0.19 unit/mg of anti-factor IIa activity, respectively. Additional experiments revealed that the anticoagulantly active aortic components were significantly present only within the intima. The above populations of heparin-like species were affinity fractionated with antithrombin. The highly active component obtained from calf cerebral microvasculature exhibited an anti-factor Xa activity of 40.7 units/mg as well as an anti-factor IIa activity of 36.8 units/mg, constituted about 4.2% of the initial mass of the starting material, and represented about 75% of the biologic potency of the starting material. The highly active component derived from calf aorta exhibited an anti-factor Xa activity of 55.4 units/mg as well as an anti-factor IIa activity of 11.3 units/mg, constituted about 0.3% of the initial mass of the starting material, and represented about 60% of the biologic potency of the starting material. The highly active cerebral microvascular species possessed a molecular weight and charge density similar to that of heparan sulfate whereas the highly active aortic species displayed a molecular weight and charge density equivalent to that of a hexadecasaccharide fragment of heparin.