THROMBIN RECEPTOR AND UROKINASE-TYPE PLASMINOGEN-ACTIVATOR ARE COLOCALIZED IN VASCULAR SMOOTH-MUSCLE CELLS DERIVED FROM HUMAN CAROTID ATHEROSCLEROTIC PLAQUES

Since the u-PA/uPAR system and thrombin are main contributors to the p rocess of proliferation and migration of vascular smooth muscle cells, which is essential in the pathogenesis and progression of atheroscler osis, we assessed the role of spatial expression of these two mediator systems on cells, derived from advanced human carotid artery plaques, We compared our results to human non-atherosclerotic tissue and as a positive control to tissue from mammary carcinoma. We have used a doub le immunolabeling approach, combining various anti-u-PA, anti-uPAR and anti-thrombin receptor antibodies, identifying smooth muscle cells, e ndothelial cells and inflammatory cells. In the carotid atheroscleroti c plaques, u-PA and uPAR immunostaining was distributed focally, prefe rentially in the fibrous cap and in the inflammatory cell-rich region, Thrombin receptor staining was distributed similar to u-PA/uPAR stain ing. With double staining, combining anti-u-PA antibodies with anti-th rombin receptor antibodies, cellular colocalisation of both u-PA and t hrombin receptor was demonstrated, which was restricted to vascular sm ooth muscle cells. Inflammatory cells, however, were mainly localised within the inflammatory cell-rich region and only stained positive for u-PA and uPAR, On the other hand in nonatherosclerotic lesions only w eak immunoreactivity for both mediator systems was detectable. Our dat a demonstrate that u-PA/uPAR and thrombin receptor are cc-expressed on smooth muscle cells in human carotid artery atherosclerotic plaque ti ssue. Conclusion not based on data in this paper.