| First Author | Wang M | Year | 2011 |
| Journal | Circulation | Volume | 123 |
| Issue | 6 | Pages | 631-9 |
| PubMed ID | 21282500 | Mgi Jnum | J:181445 |
| Mgi Id | MGI:5311318 | Doi | 10.1161/CIRCULATIONAHA.110.973685 |
| Citation | Wang M, et al. (2011) Microsomal prostaglandin e2 synthase-1 modulates the response to vascular injury. Circulation 123(6):631-9 |
| abstractText | BACKGROUND: Microsomal (m) prostaglandin (PG) E(2) synthase (S)-1 catalyzes the formation of PGE(2) from PGH(2), 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 x 10(3) 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(2) but more PGI(2) and expressed reduced tenascin-C compared with wild-type cells. Both suppression of PGE(2) and augmentation of PGI(2) 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. |
