Proteinase-activated receptor-2 mediates arterial vasodilation in diabetes.
Arterioscler Thromb Vasc Biol
; 25(11): 2349-54, 2005 Nov.
Article
em En
| MEDLINE
| ID: mdl-16141401
ABSTRACT
OBJECTIVE:
Proteinase-activated receptor-2 is widely expressed in vascular tissue and in highly vascularized organs in humans and other species. Its activation mainly causes endothelium-dependent vasorelaxation in vitro and hypotension in vivo. Here, using nonobese diabetic (NOD) mice at different disease stages, we have evaluated the role of PAR2 in the arterial vascular response during diabetes progression. METHODS ANDRESULTS:
High (NOD-II; 20 to 500 mg/dL) or severe glycosuria (NOD-III; 500 to 1000 mg/dL) provokes a progressive reduction in the response to acetylcholine paralleled by an increase in the vasodilatory response to PAR2 stimulation. Western blot and quantitative real-time polymerase chain reaction (RT-PCR) studies showed that this effect is tied to an increased expression of PAR2 coupled to cyclooxygenase-2 expression. Pharmacological dissection performed with specific inhibitors confirmed the functional involvement of cyclooxygenase-2 in PAR2 vasodilatory effect. This vasodilatory response was confirmed to be dependent on expression of PAR2 in the smooth muscle component by immunohistochemistry studies performed on aorta isolated by both NOD-III and transgenic PAR2 mice.CONCLUSIONS:
Our data demonstrate an important role for PAR2 in modulating vascular arterial response in diabetes and suggest that this receptor could represent an useful therapeutic target.
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Base de dados:
MEDLINE
Assunto principal:
Vasodilatação
/
Receptor PAR-2
/
Diabetes Mellitus Tipo 1
/
Angiopatias Diabéticas
Limite:
Animals
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Itália