title: Cell selective cardiovascular biology of microsomal prostaglandin E synthase-1.
abstract: BACKGROUND
  Global deletion of microsomal prostaglandin E synthase 1 (mPGES-1) in mice attenuates the response to vascular injury without a predisposition to thrombogenesis or hypertension. However, enzyme deletion results in cell-specific differential use by prostaglandin synthases of the accumulated prostaglandin H(2) substrate. Here, we generated mice deficient in mPGES-1 in vascular smooth muscle cells, endothelial cells, and myeloid cells further to elucidate the cardiovascular function of this enzyme.
  
  
  RESULTS
  Vascular smooth muscle cell and endothelial cell mPGES-1 deletion did not alter blood pressure at baseline or in response to a high-salt diet. The propensity to evoked macrovascular and microvascular thrombogenesis was also unaltered. However, both vascular smooth muscle cell and endothelial cell mPGES-1-deficient mice exhibited a markedly exaggerated neointimal hyperplastic response to wire injury of the femoral artery in comparison to their littermate controls. The hyperplasia was associated with increased proliferating cell nuclear antigen and tenascin-C expression. In contrast, the response to injury was markedly suppressed by myeloid cell depletion of mPGES-1 with decreased hyperplasia, leukocyte infiltration, and expression of proliferating cell nuclear antigen and tenascin-C. Conditioned medium derived from mPGES-1-deficient macrophages less potently induced vascular smooth muscle cell proliferation and migration than that from wild-type macrophages.
  
  
  CONCLUSIONS
  Deletion of mPGES-1 in the vasculature and myeloid cells differentially modulates the response to vascular injury, implicating macrophage mPGES-1 as a cardiovascular drug target.
authors.affiliation: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Lihong
authors.initials: L
authors.lastname: Chen
authors.forename: Guangrui
authors.initials: G
authors.lastname: Yang
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Xu
authors.forename: Gregory
authors.initials: G
authors.lastname: Grant
authors.forename: John A
authors.initials: JA
authors.lastname: Lawson
authors.forename: Mohammad
authors.initials: M
authors.lastname: Bohlooly-Y
authors.forename: Garret A
authors.initials: GA
authors.lastname: FitzGerald
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D001794:Blood Pressure / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology*; D005260:Female; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000201:enzymology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008861:Microsomes / Q000201:enzymology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D022423:Myeloid Cells / Q000166:cytology / Q000201:enzymology*; D061251:Primary Cell Culture; D000071876:Prostaglandin-E Synthases; D013379:Substrate Specificity / Q000502:physiology; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology; D014652:Vascular Diseases / Q000378:metabolism / Q000473:pathology
chemical_list: D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse