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

ABSTRACT: Microsomal (m) prostaglandin (PG) E? synthase (S)-1 catalyzes the formation of PGE? from PGH?, 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.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 PGE? but more PGI? and expressed reduced tenascin-C compared with wild-type cells. Both suppression of PGE? and augmentation of PGI? attenuate tenascin-C expression and vascular smooth muscle cell proliferation and migration in vitro.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.

SUBMITTER: Wang M 

PROVIDER: S-EPMC3827687 | biostudies-other | 2011 Feb

REPOSITORIES: biostudies-other