Nitric oxide-dependent synthesis of vascular endothelial growth factor is impaired by high glucose

Life Sciences
Józef DulakAlicja Józkowicz

Abstract

Synthesis of vascular endothelial growth factor (VEGF), the major angiogenic molecule, is induced by nitric oxide (NO) in various cell types, including vascular smooth muscle cells (VSMC). Therefore, compounds which inhibit NO generation can also influence VEGF synthesis. Here we investigated the effect of increased glucose concentration (25 mM vs. 5.5 mM) on cytokine-induced VEGF synthesis in rat VSMC. The cells growing in the medium containing 5.5 mM glucose and exposed to IL-1-beta, TNF-alpha and IFN-gamma induced expression of an inducible isoform of nitric oxide synthase (NOS II). This is followed by generation of NO and the concomitant expression of VEGF gene and release of VEGF protein. In contrast, 25 mM glucose impaired induction of NOS II expression and thus NO synthesis was lower than in 5.5 mM glucose. Consequently, the VEGF promoter activation was attenuated, resulting in decreased mRNA synthesis and lower production of VEGF protein. The results indicate that abnormally high concentrations of glucose can impair generation of NO and the NO-dependent VEGF synthesis. This may play a role in the development and progression of vascular dysfunctions in cardiovascular diseases.

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Citations

Jun 26, 2008·Antioxidants & Redox Signaling·Agnieszka LobodaJozef Dulak
Jul 15, 2015·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·S JoshiA Sharma
May 9, 2012·Environmental Toxicology and Pharmacology·Guoyan LiuChunyan Chai
Oct 4, 2011·The Journal of Surgical Research·Daniela PalmieriDomenico Palombo
Dec 15, 2004·Biochemical and Biophysical Research Communications·Jarosław CisowskiJózef Dulak

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