Cell death-associated ADAMTS4 and versican degradation in vascular tissue.
High blood flow through baboon polytetrafluorethylene aorto-iliac grafts increases neointimal vascular smooth muscle cell (SMC) death, neointimal atrophy, and cleavage of versican to generate the DPEAAE neoepitope, a marker of ADAMTS-mediated proteolysis. In this study, we have determined the effect of high blood flow on transcript abundance in the neointima for ADAMTS1, -4, -5, -8, -9, -15, and -20. We found that after 24 hr of flow, the mRNA for ADAMTS4 was significantly increased, whereas that for the other family members was unchanged. Because vascular SMC death is markedly increased in the graft after 24 hr of high flow, we next examined the possibility that the ADAMTS4 induction and the cell death are causally related. The addition of Fas ligand to SMC cultures increased both ADAMTS4 mRNA and cell death approximately 5-fold, consistent with the idea that ADAMTS4-dependent cleavage of versican may be partly responsible for cell death and tissue atrophy under these conditions.
Kenagy
Richard D
RD
Center for Cardiovascular Biology, PO Box 358050, University of Washington School of Medicine, 815 Mercer St., Seattle, WA 98109. rkenagy@u.washington.edu.
Min
Seung-Kee
SK
Clowes
Alexander W
AW
Sandy
John D
JD
D051722:ADAM Proteins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000503:physiopathology; D001013:Aorta, Thoracic / Q000378:metabolism; D001284:Atrophy; D001807:Blood Vessel Prosthesis; D016923:Cell Death; D002478:Cells, Cultured; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000494:pharmacology; D006801:Humans; D007083:Iliac Artery / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D048548:Papio cynocephalus; D011138:Polytetrafluoroethylene; D012333:RNA, Messenger / Q000096:biosynthesis; D012039:Regional Blood Flow; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D053675:Versicans / Q000378:metabolism*
D053222:Fas Ligand Protein; D012333:RNA, Messenger; D053675:Versicans; D011138:Polytetrafluoroethylene; D051722:ADAM Proteins