Furin and membrane type-1 metalloproteinase mRNA levels and activation of metalloproteinase-2 are associated with arterial remodeling

Matrix metalloproteinase (MMP) activation is an: essential feature of patho logical and physiological arterial enlargement or shrinkage. Recently, furi n-activated membrane type-1 MMP (MT1-MMP) was identified as the in vivo act ivator of MMP2 in mice. Although arterial enlargement and shrinkage are imp ortant in several pathological processes, this proprotein convertase-MT1-MM P axis has not been described during arterial remodeling. In rabbit femoral and carotid arteries, we report an increase in furin and MT1-MMP mRNA leve ls before and at the onset of arterial remodeling followed by an increase i n activated MMP2. This reveals the presence of the proprotein convertase-MT 1-MMP axis in flow-induced arterial remodeling and identifies furin as a po ssible target for local intervention in pathological arterial remodeling. ( C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.