IMMUNOLOCALIZATION OF THROMBOSPONDIN-1 IN HUMAN ATHEROSCLEROTIC AND RESTENOTIC ARTERIES

Experimental studies have implicated a functional role for the extrace llular matrix glycoprotein thrombospondin-1 (TSP-1) in vascular smooth muscle cell proliferation and migration. We therefore sought to deter mine if TSP-1 might represent a specific component of the fibroprolife rative tissue typically associated with restenosis lesions from human coronary and peripheral arteries. Positive immunostaining for TSP-1 wa s limited to hypocellular plaques typical of primary atherosclerosis; in contrast, such staining was nearly absent from the loose extracellu lar matrix of the fibroproliferative tissue typical of restenotic lesi ons. Only a small fraction of vascular smooth muscle cells in either p rimary or restenotic lesions demonstrated a cellular staining pattern for TSP-1, which was also observed in control studies performed in cel l culture and in atherosclerotic rabbit arteries examined 3 days after experimental balloon angioplasty. Double-staining for TSP-1 and proli ferating cell nuclear antigen in studies of human beings disclosed tha t only a small portion of proliferating cell nuclear antigen-positive cells also stained for TSP-1. The observations made in this series of specimens thus indicate that TSP-1 is not a major component of the ext racellular matrix of human restenotic tissues, even when such specimen s demonstrate evidence of hypercellularity or ongoing cellular prolife ration. Because most restenosis specimens, however, were retrieved gre ater than or equal to 1 month after the primary intervention, a functi onal role for TSP-1 in smooth muscle cell proliferation or migration a t the early stages of lesion development is still possible.