The response of smooth muscle cells to α-thrombin depends on its arterial origin: comparison among different species

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Abstract

Background

Thrombin plays a pivotal role in the pathogenesis of arterial thrombosis and exerts a wide spectrum of effects on the cells of vessel walls.

Methods

In this paper we focus on the direct role of thrombin as a mitogen for smooth muscle cells (SMCs) derived from different vessels from the vascular tree (coronary artery, aorta, carotid artery and pulmonary artery) of different species (human and pig). All cell populations examined responded mitogenically to α-thrombin, however the extent of this response was dependent on both vascular origin and the species from which vessels were derived.

Results

Thrombin (1-100 nmol L−1) induced DNA synthesis ranging from 1.5- to 4-fold baseline depending on cell type. Porcine coronary SMCs showed the highest response to thrombin (100 nmol L−1) in terms of protein and DNA synthesis (4.0 ± 0.2-fold) and cell division (53.4 ± 8.8%) among the tested cells. In these cells recombinant (r)-hirudin, a specific thrombin inhibitor, exhibited maximal effectiveness to block the mitogenic effect of thrombin. Human SMC response ([3H]-thymidine incorporation) to either sera or thrombin was lower than that of porcine cells. In contrast, c-fos mRNA levels induced by thrombin in human SMCs were higher than those induced in porcine cells. In human cells, thrombin elicited an overexpression of c-fos and a lower rate of [3H]-thymidine incorporation than in porcine cells. Insulin-like growth factor I but not insulin showed additive mitogenic effects with thrombin in human coronary SMCs. The response of these cells to thrombin from different sources was a function of thrombin specific activity.

Conclusion

These results suggest that the cell system chosen to check thrombin mitogenicity not only determines thrombin quantitative effects but also may affect the effectiveness of an inhibitor to block its biological activity.

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