Cell selective cardiovascular biology of microsomal prostaglandin E synthase-1.
Circulation
; 127(2): 233-43, 2013 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-23204105
ABSTRACT
BACKGROUND:
Global deletion of microsomal prostaglandin E synthase 1 (mPGES-1) in mice attenuates the response to vascular injury without a predisposition to thrombogenesis or hypertension. However, enzyme deletion results in cell-specific differential use by prostaglandin synthases of the accumulated prostaglandin H(2) substrate. Here, we generated mice deficient in mPGES-1 in vascular smooth muscle cells, endothelial cells, and myeloid cells further to elucidate the cardiovascular function of this enzyme. METHODS ANDRESULTS:
Vascular smooth muscle cell and endothelial cell mPGES-1 deletion did not alter blood pressure at baseline or in response to a high-salt diet. The propensity to evoked macrovascular and microvascular thrombogenesis was also unaltered. However, both vascular smooth muscle cell and endothelial cell mPGES-1-deficient mice exhibited a markedly exaggerated neointimal hyperplastic response to wire injury of the femoral artery in comparison to their littermate controls. The hyperplasia was associated with increased proliferating cell nuclear antigen and tenascin-C expression. In contrast, the response to injury was markedly suppressed by myeloid cell depletion of mPGES-1 with decreased hyperplasia, leukocyte infiltration, and expression of proliferating cell nuclear antigen and tenascin-C. Conditioned medium derived from mPGES-1-deficient macrophages less potently induced vascular smooth muscle cell proliferation and migration than that from wild-type macrophages.CONCLUSIONS:
Deletion of mPGES-1 in the vasculature and myeloid cells differentially modulates the response to vascular injury, implicating macrophage mPGES-1 as a cardiovascular drug target.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Oxirredutases Intramoleculares
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Células Mieloides
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Células Endoteliais
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Macrófagos
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Microssomos
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Músculo Liso Vascular
Limite:
Animals
Idioma:
En
Revista:
Circulation
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos