Vascular smooth muscle cells efficiently activate a new proteinase cascade involving plasminogen and fibronectin.
The plasminogen/plasmin system is involved in vascular wall remodeling after injury, through extracellular matrix (ECM) degradation and proteinase activation. Vascular smooth muscle cells (VSMCs) synthesize various components of the plasminogen/plasmin system. We investigated the conversion of plasminogen into plasmin in primary cultured rat VSMCs. VSMCs efficiently converted exogenous plasminogen into plasmin in a time- and dose-dependent manner. We measured plasmin activity by monitoring the hydrolysis of Tosyl-G-P-R-Mca, a fluorogenic substrate of plasmin. Cell-mediated plasmin activation was associated with the degradation of ECM, as revealed by fibronectin proteolysis. Plasmin also activated a proteinase able to hydrolyze Mca-P-L-G-L-Dpa-A-R-NH(2), a fluorogenic substrate of matrix metalloproteinases (MMPs). However, this proteinase was not inhibited by an MMP inhibitor. Furthermore, this proteinase displayed similar biochemical and pharmacological properties to fibronectin-proteinase, a recently identified zinc-dependent metalloproteinase located in the gelatin-binding domain of fibronectin. These results show that VSMCs convert exogenous plasminogen into plasmin in their pericellular environment. By hydrolyzing matrix protein plasmin activates a latent metalloproteinase that differs from MMP, fibronectin-proteinase. This metalloproteinase may participate to vascular wall remodeling, in concert with other proteinases.
Houard
Xavier
X
INSERM Unité 36, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
Monnot
Catherine
C
Dive
Vincent
V
Corvol
Pierre
P
Pagano
Maurice
M
D000818:Animals; D001013:Aorta, Thoracic; D004789:Enzyme Activation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D010958:Plasminogen / Q000096:biosynthesis* / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D014945:Wound Healing / Q000502:physiology
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D012333:RNA, Messenger; D010958:Plasminogen; D005341:Fibrinolysin; D020782:Matrix Metalloproteinases