title: Gαq G proteins modulate MMP-9 gelatinase during remodeling of the murine femoral artery.
abstract: BACKGROUND
  Vessels heal after injury and G protein-coupled receptors are involved in the vascular smooth muscle cell proliferation required to form intimal hyperplasia. We have previously identified the role of Gαq in vascular smooth muscle cell proliferation in vitro. This study now examines the role of Gαq in the developing intimal hyperplasia in a murine model and the impact of disruption of Gαq signaling on intimal hyperplasia development.
  
  
  METHODS
  We employed a murine femoral wire injury model in which a micro-wire is passed through a branch of the femoral artery and used to denude the common femoral artery. We perfusion-fixed specimens and stained sections with hematoxylin-eosin and Movat's stains such that morphometric analysis could be performed using an Image-Pro system. We also harvested additional specimens of femoral artery and snap-froze them for Western blotting or zymography, to allow for the study of G protein expression and both protease expression and activity. We used contralateral vessels as controls. We immersed additional vessels in pluronic gel containing the chemical Gαq G protein inhibitors GP-2A, siRNA to Gαq or adenovirus containing mutant inactive Gαq.
  
  
  RESULTS
  Gαq expression increased in a time-dependent manner after femoral artery injury. Sham-operated vessels did not produce such a response. Inhibition of Gαq reduced cell proliferation without affecting cell migration. Interruption of Gαq signaling also inhibited the development of intimal hyperplasia. Inhibition of Gαq did not alter peak urinary-type plasminogen activator activity and expression, but did increase early plasminogen activator inhibitor-1 activity and expression. Inhibition of Gαq reduced peak metalloproteinase (MMP)-9 activity at Day 3 but did not influence peak MMP-2 activity at Day 7. Protein expression for MMP-9 was also decreased, but that of MMP-2 was not affected. There were no changes in the expression or the activity of the respective inhibitors for MMP-9 and MMP-2, and tissue inhibitor of metalloproteinases-1 and -2.
  
  
  CONCLUSIONS
  These data demonstrate that femoral wire injury in the mouse is associated with a time-dependent increase in Gαq expression. Inhibition of Gαq alters cell proliferation and is associated with decreased MMP-9 expression and activity.
authors.affiliation: Vascular Biology and Therapeutics Program, The Methodist Hospital Research Institute, Houston, Texas.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zou
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Fu
authors.forename: Mark G
authors.initials: MG
authors.lastname: Davies
mesh_terms: D000818:Animals; D005263:Femoral Artery / Q000473:pathology*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000502:physiology*; D006965:Hyperplasia; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D017539:Tunica Intima / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D043802:GTP-Binding Protein alpha Subunits, Gq-G11