Cyclooxygenase-2 in endothelial and vascular smooth muscle cells restrains atherogenesis in hyperlipidemic mice.
Circulation
; 129(17): 1761-9, 2014 Apr 29.
Article
en En
| MEDLINE
| ID: mdl-24519928
ABSTRACT
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 ANDRESULTS:
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, α-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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Endotelio Vascular
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Aterosclerosis
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Ciclooxigenasa 2
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Hiperlipidemias
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Músculo Liso Vascular
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Circulation
Año:
2014
Tipo del documento:
Article