Increased expression of gelatinases and alteration of basement membrane inrat soleus muscle following femoral artery ligation

Acute severe muscle ischaemia is characterized by significant remodelling o f basement membranes of myofibres. It was hypothesized that peripheral arte ry insufficiency is accompanied by similar muscle extracellular matrix (ECM ) changes involving matrix metalloproteinase gelatinases. Using a model of femoral artery ligation, both gelatinase activity and basement membrane com ponent degradation were studied in hindlimb skeletal muscles. SDS-PAGE zymo graphy of muscle homogenates showed that acute moderate ischaemia was follo wed by a significant transient increase in expression of 72- and 92-kDa gel atinases during 48 h; the latter probably originated from inflammatory cell s. In situ zymography showed that this increase occurred chiefly at the per iphery of myofibres. Immunolocalization demonstrated 72-kDa gelatinase in i nterspaces and at the periphery of myofibres, and suggested that this enzym e may explain the gelatinolytic activities found by in situ zymography. Typ e IV collagen and laminin staining showed that the gelatinase expression in crease correlated with dramatic basement membrane component alterations. Ou r data show that even moderate ischaemia results in significant muscle base ment membrane remodelling due to matrix degrading enzymes matrix metallopro teinases (MMP) gelatinases.