Nitric Oxide and Cyclic GMP Increase the Expression of Matrix Metalloproteinase-9 in Vascular Smooth Muscle

2003 ◽  
Vol 307 (1) ◽  
pp. 429-436 ◽  
Author(s):  
Marcelo Marcet-Palacios ◽  
Kathryn Graham ◽  
Carol Cass ◽  
A. Dean Befus ◽  
Irvin Mayers ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Matrix Metalloproteinase ◽  
Vascular Smooth Muscle ◽  
Cyclic Gmp ◽  
Matrix Metalloproteinase 9 ◽  
Metalloproteinase 9

scholarly journals The multifunctional Ca2+/calmodulin-dependent kinase II regulates vascular smooth muscle migration through matrix metalloproteinase 9

2012 ◽  
Vol 302 (10) ◽  
pp. H1953-H1964 ◽  
Author(s):  
Jason A. Scott ◽  
Litao Xie ◽  
Hui Li ◽  
Weiwei Li ◽  
Julie B. He ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Matrix Metalloproteinase ◽  
Vascular Smooth Muscle ◽  
Posttranscriptional Regulation ◽  
Resistant Mutant ◽  
Matrix Metalloproteinase 9 ◽  
Tnf Α ◽  
Metalloproteinase 9

The multifunctional CaMKII has been implicated in vascular smooth muscle cell (VSMC) migration, but little is known regarding its downstream targets that mediate migration. Here, we examined whether CaMKII regulates migration through modulation of matrix metalloproteinase 9 (MMP9). Using CaMKIIδ−/−mice as a model system, we evaluated migration and MMP9 regulation in vitro and in vivo. After ligation of the common carotid artery, CaMKII was activated in the neointima as determined by oxidation and autophosphorylation. We found that MMP9 was robustly expressed in the neointima and adventitia of carotid-ligated wild-type (WT) mice but was barely detectable in CaMKIIδ−/−mice. The perimeter of the external elastic lamina, a correlate of migration-related outward remodeling, was increased in WT but not in CaMKIIδ−/−mice. Migration induced by serum, platelet-derived growth factor, and tumor necrosis factor-α (TNF-α) was significantly decreased in CaMKIIδ−/−as compared with WT VSMCs, but migration was rescued with adenoviral overexpression of MMP9 in CaMKIIδ−/−VSMCs. Likewise, overexpression of CaMKIIδ in CaMKIIδ−/−VSMCs increased migration, whereas an oxidation-resistant mutant of CaMKIIδ did not. TNF-α strongly induced CaMKII oxidation and autophosphorylation as well as MMP9 activity, mRNA, and protein levels in WT, but not in CaMKIIδ−/−VSMC. Surprisingly, TNF-α strongly induced MMP9 promoter activity in WT and CaMKIIδ−/−VSMC. However, the MMP9 mRNA stability was significantly decreased in CaMKIIδ−/−VSMC. Our data demonstrate that CaMKII promotes VSMC migration through posttranscriptional regulation of MMP9 and suggest that CaMKII effects on MMP9 expression may be a therapeutic pathway in vascular injury.

Nitric Oxide Inhibition Increases Aortic Wall Matrix Metalloproteinase-9 Expression

2002 ◽  
Vol 104 (1) ◽  
pp. 15-21 ◽  
Author(s):  
Matthew J. Eagleton ◽  
David A. Peterson ◽  
Vita V. Sullivan ◽  
Karen J. Roelofs ◽  
John A. Ford ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Matrix Metalloproteinase ◽  
Aortic Wall ◽  
Matrix Metalloproteinase 9 ◽  
Nitric Oxide Inhibition ◽  
Metalloproteinase 9 ◽  
Oxide Inhibition
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