EXPRESSION OF MATRIX-DEGRADING ENZYMES IN PULMONARY VASCULAR REMODELING IN THE RAT

Exposure of rats to hypoxia causes pulmonary arterial remodeling, whic h is partly reversible after return to air. We hypothesized that degra dation of excess collagen in remodeled pulmonary arteries in the posth ypoxic period is mediated by endogenous matrix metalloproteinases (MMP s). Total proteolytic, collagenolytic, and gelatinolytic activities, l evels of stromelysin-1 and tissue inhibitor of metalloprotease-1 (TIMP -1), and immunolocalization of stromelysin-1 in main pulmonary arterie s were determined after exposure of rats to 10% O-2 for 10 days follow ed by normoxia. We observed transient increases in total proteolytic, collagenolytic, and gelatinolytic activities and expression of similar to 72-, 68-, and 60-kDa gelatinases by zymography within 3 days of ce ssation of hypoxide exposure. The level of TIMP-1 increased as the str omelysin-1 level increased. Immunoreactive stromelysin-1 was localized predominantly in the luminal region of normal and hypertensive pulmon ary arteries. These results are consistent with the notion that endoge nous MMPs may mediate the breakdown of excess collagen in remodeled pu lmonary arteries during the early posthypoxic period.