In vivo antithrombotic properties of a heparin from the oocyte test cells of the sea squirt Styela plicata(Chordata-Tunicata)

Abstract

In the ascidian Styela plicata, the oocytes are surrounded by two types of accessory cells named follicle cells and test cells. A heparin-like substance with an anticoagulant activity equivalent to 10% of mammalian heparin and about 5% as potent as the mammalian counterpart for the inhibition of thrombin by antithrombin was isolated from the oocyte test cells. In the present study, we compared the antithrombotic and hemorrhagic effects of sea squirt oocyte test cell heparin with those of porcine heparin in rat models of venous thrombosis and blood loss. Intravenous administration of the oocyte test cell heparin to Wistar rats (both sexes, weighing ~300 g, N = 4 in each group) at a dose of 5.0 mg/kg body weight, which produced a 1.8-fold increase in plasma activated partial thromboplastin time, inhibited thrombosis by 45 ± 13.5% (mean ± SD) without any bleeding effect. The same dose of porcine heparin inhibited thrombosis by 100 ± 1.4%, but produced a blood loss three times greater than that of the saline-treated control. However, 10-fold reduction of the dose of porcine heparin to 0.5 mg/ kg body weight, which produced a 5-fold increase in plasma-activated partial thromboplastin time, inhibited thrombosis by 70 ± 13% without any bleeding effect. The antithrombotic properties of a new heparin isolated from test cells of the sea squirt S. plicata, reported here for the first time, indicate that, although sea squirt oocyte test cell heparin was a poor anticoagulant compared to porcine heparin, it had a significant antithrombotic effect without causing bleeding.

Urochordate Histoincompatible Interactions Activate Vertebrate-Like Coagulation System Components

“…Furthermore, results from the solitary ascidian Styela plicata , support potential roles of ascidian-borne heparin in coagulation. A heparin-like substance that was isolated from this species [32] showed 10% anticoagulant potency compared to mammalian counterpart and 5% potency in thrombin inhibition activity [33]. Similarly, dermatan sulfates with anticoagulant activity were described in the ascidians S. plicata and H. pyriformis [34].…”

Glycosaminoglycans analogs from marine invertebrates: structure, biological effects, and potential as new therapeutics

“…S. plicata heparin at a dose of 4 mg/kg body weight, which is above the dose required to prevent thrombus on an animal experimental model did not increase the amount of blood loss in comparison with the saline control. In contrast, mammalian heparin, compared to the control, increased blood loss almost 2-fold (Cardilo-Reis et al, 2006). …”

Antioxidant and TNF-α Inducing Ability of Styela plicata Extracts

“…Several researches such as antithrombotic properties of a heparin [2], antimicrobial peptide [23], and antiviral activity [7] of S. plicata have been reported. In this paper, the antioxidative and tumor necrosis factor (TNF)-α inducing ability of the extracts of S. plicata with four different solvents were evaluated.…”