Immunolocalization of thrombospondin-1 in human atherosclerotic and restenotic arteries.
Experimental studies have implicated a functional role for the extracellular matrix glycoprotein thrombospondin-1 (TSP-1) in vascular smooth muscle cell proliferation and migration. We therefore sought to determine if TSP-1 might represent a specific component of the fibroproliferative tissue typically associated with restenosis lesions from human coronary and peripheral arteries. Positive immunostaining for TSP-1 was limited to hypocellular plaques typical of primary atherosclerosis; in contrast, such staining was nearly absent from the loose extracellular matrix of the fibroproliferative tissue typical of restenotic lesions. Only a small fraction of vascular smooth muscle cells in either primary or restenotic lesions demonstrated a cellular staining pattern for TSP-1, which was also observed in control studies performed in cell culture and in atherosclerotic rabbit arteries examined 3 days after experimental balloon angioplasty. Double-staining for TSP-1 and proliferating cell nuclear antigen in studies of human beings disclosed that 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 extracellular matrix of human restenotic tissues, even when such specimens demonstrate evidence of hypercellularity or ongoing cellular proliferation. Because most restenosis specimens, however, were retrieved > or =1 month after the primary intervention, a functional role for TSP-1 in smooth muscle cell proliferation or migration at the early stages of lesion development is still possible.
Riessen
R
R
Department of Medicine (Cardiology), St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA.
Kearney
M
M
Lawler
J
J
Isner
J M
JM
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D016491:Peripheral Vascular Diseases / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D012008:Recurrence; D019700:Thrombospondin 1 / Q000378:metabolism*
D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D019700:Thrombospondin 1