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Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis

Abstract

We provide anatomic and functional evidence that nicotine induces angiogenesis. We also show that nicotine accelerates the growth of tumor and atheroma in association with increased neovascularization. Nicotine increased endothelial-cell growth and tube formation in vitro, and accelerated fibrovascular growth in vivo. In a mouse model of hind-limb ischemia, nicotine increased capillary and collateral growth, and enhanced tissue perfusion. In mouse models of lung cancer and atherosclerosis, we found that nicotine enhanced lesion growth in association with an increase in lesion vascularity. These effects of nicotine were mediated through nicotinic acetylcholine receptors at nicotine concentrations that are pathophysiologically relevant. The endothelial production of nitric oxide, prostacyclin and vascular endothelial growth factor might have a role in these effects.

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Figure 1: Nicotine stimulates angiogenesis in vitro.
Figure 2: Nicotine enhances the angiogenic response to inflammation.
Figure 3: Nicotine stimulates angiogenesis in a mouse model of hind-limb ischemia.
Figure 4: Nicotine stimulates tumor growth in the Lewis lung cancer model.
Figure 5: Nicotine stimulates plaque growth in a mouse model of atherosclerosis.

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Acknowledgements

This study was supported by grants from the National Heart, Lung and Blood Institute (R01 HL-58638), the Tobacco Related Disease Research Program (7RT-0128), and the German Research Council (He 3044/1-1). Stanford University owns a patent on the use of nicotine for therapeutic angiogenesis, which has been licensed to Endovasc Inc. The authors are inventors of this patent, and might receive royalties from the license.

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Correspondence to John P. Cooke.

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Heeschen, C., Jang, J., Weis, M. et al. Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis. Nat Med 7, 833–839 (2001). https://doi.org/10.1038/89961

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