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Circulation. 2011 Feb 15;123(6):631-9. doi: 10.1161/CIRCULATIONAHA.110.973685. Epub 2011 Jan 31.

Microsomal prostaglandin e2 synthase-1 modulates the response to vascular injury.

Author information

  • 1Institute for Translational Medicine and Therapeutics, Department of Pharmacology, University of Pennsylvania, Philadelphia, USA. miaowang@upenn.edu

Abstract

BACKGROUND:

Microsomal (m) prostaglandin (PG) E₂ synthase (S)-1 catalyzes the formation of PGE₂ from PGH₂, a cyclooxygenase product that is derived from arachidonic acid. Previous studies in mice suggest that targeting mPGES-1 may be less likely to cause hypertension or thrombosis than cyclooxygenase-2-selective inhibition or deletion in vivo. Indeed, deletion of mPGES-1 retards atherogenesis and angiotensin II-induced aortic aneurysm formation. The role of mPGES-1 in the response to vascular injury is unknown.

METHODS AND RESULTS:

Mice were subjected to wire injury of the femoral artery. Both neointimal area and vascular stenosis were significantly reduced 4 weeks after injury in mPGES-1 knockout mice compared with wild-type controls (65.6 ± 5.7 versus 37.7 ± 5.1 × 10³ pixel area and 70.5 ± 13.4% versus 47.7 ± 17.4%, respectively; P < 0.01). Induction of tenascin-C, a proproliferative and promigratory extracellular matrix protein, after injury was attenuated in the knockouts. Consistent with in vivo rediversion of PG biosynthesis, mPGES-1-deleted vascular smooth muscle cells generated less PGE₂ but more PGI₂ and expressed reduced tenascin-C compared with wild-type cells. Both suppression of PGE₂ and augmentation of PGI₂ attenuate tenascin-C expression and vascular smooth muscle cell proliferation and migration in vitro.

CONCLUSIONS:

Deletion of mPGES-1 in mice attenuates neointimal hyperplasia after vascular injury, in part by regulating tenascin-C expression. This raises for consideration the therapeutic potential of mPGES-1 inhibitors as adjuvant therapy for percutaneous coronary intervention.

PMID:
21282500
[PubMed - indexed for MEDLINE]
PMCID:
PMC3827687
Free PMC Article
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