Heparin functions, physiological

Despite its widespread use in therapy as an anticoagulant and antilipe-mic agent, several aspects of the structure and physiological function of heparin remain obscure. However, active reseach has now contributed to a better understanding of the molecular basis for the pharmacological activity of this polysaccharide. 

The physiological function of heparin is not completely understood. It is found only in trace amounts in normal circulating blood. It exerts an antihpemic effect by releasing lipoprotein lipase from endothehal cells heparinlike proteoglycans produced by endothelial cells have anticoagulant activity. Heparin decreases platelet and inflammatory cell adhesiveness to endothelial cells, reduces the release of platelet-derived growth factor, inhibits tumor cell metastasis, and exerts an antiproliferative effect on several types of smooth muscle. 

Micromedex, lepirudin directly inhibits all actions of thrombin. It inhibits free and clot-bound thrombin without requiring endogenous cofactors. Lepirudin is not inhibited by platelet factor 4 and acts independently of antithrombin III and heparin cofactor II. It has no direct effect on platelet function, except inhibition of thrombin-induced platelet activation. No physiological inhibitor of lepirudin is known. 

Fig. 4. Radioactivity of the I4C-labelled heparin-containing hydrogel as a function of eluent and elution time. 1 distilled water, 2 physiological solution, 3 human blood plasma 101)...

The milk lipase that is activated by foaming and causes the rancidity of milk is a glycoprotein or a family of glycoproteins. It is inhibited by DFP and is specific for primary ester bonds (14), The physiological function of the lipase is mysterious since new-born animals already possess their own digestive lipases. Milk also contains a lipoprotein lipase which has the properties typical for such an enzyme it is sensitive to heparin and activated by serum proteins. This enzyme is probably serum lipoprotein lipase that has leaked into the milk (14). 

Significant physiological functions not occurring in mast cells have been found for heparin and histamine (3,4,5,6). In this form the agents are synthesized and released as required. Thus, in the intestine, in response to a meal of fat, secretion of histamine causes increased vessel permeability and fat transport, while secretion of heparin causes release of DAO to destroy the histamine in a negative feedback cycle (see Figure 8). 

Heparinase Activity. Several assays were used to follow heparinase activity. These assays followed (1) the disappearance of heparin, (2) the appearance of heparin degradation products, or (3) the loss of the physiological function of heparin in anticoagulation. The basis of these assays and explanations as to when they are routinely used are listed below. 

Sandset PM, Bendz B, Hansen JB. Physiological function of tissue factor pathway inhibitor and interaction with heparins. Haemostasis 2000 30 48-56. 

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