Cell selective cardiovascular biology of microsomal prostaglandin E synthase-1

Circulation. 2013 Jan 15;127(2):233-43. doi: 10.1161/CIRCULATIONAHA.112.119479. Epub 2012 Nov 30.


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.

Methods and 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aorta, Thoracic / cytology
  • Blood Pressure / physiology
  • Endothelial Cells / cytology
  • Endothelial Cells / enzymology*
  • Female
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / metabolism*
  • Macrophages / cytology
  • Macrophages / enzymology*
  • Male
  • Mice
  • Mice, Knockout
  • Microsomes / enzymology*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / enzymology*
  • Myeloid Cells / cytology
  • Myeloid Cells / enzymology*
  • Primary Cell Culture
  • Prostaglandin-E Synthases
  • Substrate Specificity / physiology
  • Thrombosis / metabolism
  • Thrombosis / pathology
  • Vascular Diseases / metabolism
  • Vascular Diseases / pathology


  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases
  • Ptges protein, mouse