Cilostazol Activates AMP-activated Protein Kinase and Restores Endothelial Function in Diabetes.

Cilostazol Activates AMP-activated Protein Kinase and Restores Endothelial Function in Diabetes. Research Abstract Details 

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Cilostazol Activates AMP-activated Protein Kinase and Restores Endothelial Function in Diabetes. Abstract Text:

Kunihiro Suzuki,Kohsuke Uchida,Nobuo Nakanishi,Yoshiyuki Hattori,Kunihiro Suzuki,Kohsuke Uchida,Nobuo Nakanishi,Yoshiyuki Hattori,

BackgroundEndothelial dysfunction plays a key role in atherogenesis. We investigated whether AMP-activated protein kinase (AMPK) activity is a downstream mediator of the beneficial effects of cilostazol on vascular endothelial cells and whether cilostazol might reverse endothelial dysfunction in diabetic rats.Methods and ResultsTreatment of human umbilical vein endothelial cells (HUVECs) with cilostazol resulted in time-dependent activation of AMPK, as monitored by phosphorylation of AMPK and its down-stream target, acetyl-CoA carboxylase (ACC). Activation of AMPK by cilostazol was through signaling pathway independent of cyclic AMP and caused phosphorylation of endothelial nitric oxide synthase (eNOS), leading to increased production of nitric oxide (NO), while inhibiting cytokine-induced nuclear factor-kappaB (NF-kappaB) activation, leading to suppression of VCAM-1 gene expression. Significantly reduced eNOS activity and NO production in response to cilostazol and attenuation of cilostazol-induced inhibition of NF-kappaB activation were observed in cells treated with AMPK siRNA. We also demonstrated that administration of cilostazol to diabetic rats significantly restored endothelium-dependent vasodilation. Furthermore, treatment of diabetic rats with cilostazol increased tetrahydrobiopterin (BH4) levels in the aorta. Thus, recovery of BH4 following administration of cilostazol might also contribute to restoration of endothelial function in diabetic rats.ConclusionsOur findings suggest that the beneficial effects of cilostazol on endothelial function may be due to AMPK activation. Restoration of endothelial dysfunction in diabetic rats by cilostazol is at least partly attributed to amelioration of biopterin metabolism in the aorta.American Journal of Hypertension (2008) doi:10.1038/ajh.2007.96American Journal of Hypertension (2008); 21 4. 451-457 doi:10.1038/ajh.2008.6.

Cilostazol Activates AMP-activated Protein Kinase and Restores Endothelial Function in Diabetes. Publishing Authors By Initials

K Suzuki,K Uchida,N Nakanishi,Y Hattori,K Suzuki,K Uchida,N Nakanishi,Y Hattori,

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Cilostazol Activates AMP-activated Protein Kinase and Restores Endothelial Function in Diabetes. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: American journal of hypertension : journal of the

VOLUME: 21

Page Numbers: 451-7

Journal Abbreviation: Am. J. Hypertens.

ISSN: 0895-7061

DAY: 7

MONTH: 02

YEAR: 2008

Cilostazol Activates AMP-activated Protein Kinase and Restores Endothelial Function in Diabetes. Information

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LANGUAGE: eng

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AFFILIATION: 1Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.

Country: United States

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MEDLINETA: Am J Hypertens

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