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 pathological and physiological arterial enlargement or shrinkage. Recently, furin-activated membrane type-1 MMP (MT1-MMP) was identified as the in vivo activator of MMP2 in mice. Although arterial enlargement and shrinkage are important in several pathological processes, this proprotein convertase-MT1-MMP axis has not been described during arterial remodeling. In rabbit femoral and carotid arteries, we report an increase in furin and MT1-MMP mRNA levels before and at the onset of arterial remodeling followed by an increase in activated MMP2. This reveals the presence of the proprotein convertase-MT1-MMP axis in flow-induced arterial remodeling and identifies furin as a possible target for local intervention in pathological arterial remodeling.
de Kleijn
D P
DP
Experimental Cardiology Laboratory, University Medical Center, Utrecht, The Netherlands. d.dekleijn@hli.azu.nl
Sluijter
J P
JP
Smit
J
J
Velema
E
E
Richard
W
W
Schoneveld
A H
AH
Pasterkamp
G
G
Borst
C
C
D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D002339:Carotid Arteries / Q000166:cytology / Q000201:enzymology* / Q000502:physiology* / Q000601:surgery; D004789:Enzyme Activation; D004790:Enzyme Induction; D005263:Femoral Artery / Q000166:cytology / Q000201:enzymology* / Q000502:physiology* / Q000601:surgery; D045683:Furin; D007150:Immunohistochemistry; D008026:Ligation; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D012039:Regional Blood Flow; D013381:Subtilisins / Q000235:genetics*
D012333:RNA, Messenger; D013381:Subtilisins; D045683:Furin; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2