UP-REGULATION OF BASEMENT MEMBRANE-DEGRADING METALLOPROTEINASE SECRETION AFTER BALLOON INJURY OF PIG CAROTID ARTERIES

Basement membrane-degrading metalloproteinases (gelatinases) appear ne cessary for vascular smooth muscle cell migration and proliferation in culture and for intimal migration of cells after balloon injury to th e rat carotid artery. We investigated in the present study the secreti on of gelatinases from pig carotid artery tissue after balloon injury. Segments of injured artery and segments proximal and distal to the ar ea of injury were removed 3, 7, and 21 days after balloon dilatation. Medial explants from these segments were then cultured for 3 days, and the serum-free conditioned media were subjected to gelatin zymography . Production of 72- and 95-kD gelatinases was quantified by densitomet ry. Balloon-injured segments secreted significantly more 72- and 95-kD gelatinase than did paired distal segments at all time points. Releas e of both gelatinase activities was increased at 3 and 7 days relative to segments from uninjured arteries but declined again by 21 days aft er balloon injury. Similar results were found for gelatinase levels in extracts of arterial tissue. Consistent with the protein secretion da ta, in situ hybridization demonstrated that the mRNAs for both gelatin ases were upregulated after balloon injury. Expression was prominent i n medial smooth muscle cells, particularly around foci of necrosis, an d in neointimal cells 3 and 7 days after balloon injury; 72-kD gelatin ase mRNA persisted after 21 days and was prominent in regrown endothel ial cells. The upregulation of gelatinase activity paralleled the time course of smooth muscle cell migration and proliferation in this mode l. We conclude that increased gelatinase production occurs in response to balloon injury and may play a role in permitting migration and pro liferation of vascular smooth muscle cells.