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Osaka City Med J. 2009 Dec;55(2):71-80.

Phosphatidylinositol 3-kinase/Akt pathway regulates inflammatory mediators-induced calcification of human vascular smooth muscle cells.

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Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University, Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.



Vascular calcification is a clinically significant component of atherosclerosis and may be promoted by inflammatory stimuli. Phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is involved in the regulation of cell metabolism, survival, migration, and inflammatory responses in various cell types.


In this study, we investigated the roles of PI3K/Akt signaling pathway in human vascular smooth muscle cell (HVSMC) calcification induced by the inflammatory mediators (IM) including interferon-gamma, tumor necrosis factor-alpha, oncostatin M, and 1alpha,25-dihydroxyvitamin D3.


Pharmacological inhibition of PI3K with wortmannin dose-dependently increased IM-induced HVSMC calcification. IM-induced expression of alkaline phosphatase (ALP) in HVSMC was also augmented by wortmannin, while wortmannin did not induce apoptosis of HVSMCs in the presence or absence of IM. Moreover, wortmannin inhibited Akt activation in HVSMC by shortterm exposure to IM. Overexpression of wild-type or dominant-negative forms of Akt significantly attenuated or enhanced IM-induced ALP expression in HVSMC, respectively. Furthermore, suppression of Akt with siRNA significantly intensified IM-induced ALP expression in HVSMC.


These data suggest that PI3K/Akt pathway may play an inhibitory role in IM-induced HVSMC calcification through regulating ALP expression.

[Indexed for MEDLINE]

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