| First Author | Tang SY | Year | 2014 |
| Journal | Circulation | Volume | 129 |
| Issue | 17 | Pages | 1761-9 |
| PubMed ID | 24519928 | Mgi Jnum | J:221694 |
| Mgi Id | MGI:5641320 | Doi | 10.1161/CIRCULATIONAHA.113.007913 |
| Citation | Tang SY, et al. (2014) Cyclooxygenase-2 in endothelial and vascular smooth muscle cells restrains atherogenesis in hyperlipidemic mice. Circulation 129(17):1761-9 |
| abstractText | BACKGROUND: Placebo-controlled trials of nonsteroidal anti-inflammatory drugs selective for inhibition of cyclooxygenase-2 (COX-2) reveal an emergent cardiovascular hazard in patients selected for low risk of heart disease. Postnatal global deletion of COX-2 accelerates atherogenesis in hyperlipidemic mice, a process delayed by selective enzyme deletion in macrophages. METHODS AND RESULTS: In the present study, selective depletion of COX-2 in vascular smooth muscle cells and endothelial cells depressed biosynthesis of prostaglandin I2 and prostaglandin E2, elevated blood pressure, and accelerated atherogenesis in Ldlr knockout mice. Deletion of COX-2 in vascular smooth muscle cells and endothelial cells coincided with an increase in COX-2 expression in lesional macrophages and increased biosynthesis of thromboxane. Increased accumulation of less organized intimal collagen, laminin, alpha-smooth muscle actin, and matrix-rich fibrosis was also apparent in lesions of the mutants. CONCLUSIONS: Although atherogenesis is accelerated in global COX-2 knockouts, consistent with evidence of risk transformation during chronic nonsteroidal anti-inflammatory drug administration, this masks the contrasting effects of enzyme depletion in macrophages versus vascular smooth muscle cells and endothelial cells. Targeting delivery of COX-2 inhibitors to macrophages may conserve their efficacy while limiting cardiovascular risk. |
