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 AND RESULTS: 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.

Roviezzo, F., Bucci, M., Brancaleone, V., DI LORENZO, A., Geppetti, P., Farneti, S., et al. (2005). Proteinase-activated receptor-2 mediates arterial vasodilation in diabetes. ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY, 25(11), 2349-2354 [10.1161/01.ATV.0000184770.01494.2e].

Proteinase-activated receptor-2 mediates arterial vasodilation in diabetes

LUNGARELLA, G.;
2005-01-01

Abstract

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 AND RESULTS: 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.
2005
Roviezzo, F., Bucci, M., Brancaleone, V., DI LORENZO, A., Geppetti, P., Farneti, S., et al. (2005). Proteinase-activated receptor-2 mediates arterial vasodilation in diabetes. ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY, 25(11), 2349-2354 [10.1161/01.ATV.0000184770.01494.2e].
File in questo prodotto:
File Dimensione Formato  
ATVB 2005. Roviezzo .pdf

non disponibili

Tipologia: Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 284.66 kB
Formato Adobe PDF
284.66 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/21414
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo