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Angiotensinogen impairs angiogenesis in the chick chorioallantoic membrane

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Abstract

Angiotensinogen shares with other members of the serine protease inhibitor (serpin) family antiangiogenic properties. Angiotensinogen inhibits in vitro endothelial cell proliferation, and is antiangiogenic in ovo in the chick chorioallantoic membrane assay. The cellular mode of action of angiotensinogen has been studied by applying purified human angiotensinogen or Chinese hamster ovary cells producing recombinant angiotensinogen onto the developing chorioallantoic membrane. Vessel density of the control and angiotensinogen-treated areas was quantitated by using Sambucus nigra lectin, a specific endothelial cell marker. After 48 h of angiotensinogen treatment by either applying purified angiotensinogen or angiotensinogen-producing Chinese hamster ovary cells, there was a 70% decrease in mesodermic vessel density in comparison to the control sections. Angiotensinogen treatment induced a strong decrease in endothelial cell proliferation of the chorioallantoic membrane vasculature, as shown by incorporation of bromo-deoxyuridine. Two days after local angiotensinogen treatment, increased apoptosis of endothelial cells of mesodermal blood vessels was detected by transferase-mediated deoxyuridine triphosphate nick end labeling assay. As assessed by in situ hybridization, the gene expression pattern of the main vascular growth factors and their receptors was not altered by angiotensinogen. Angiotensinogen, therefore, impairs angiogenesis without altering the expression level of vascular growth factors through the induction of apoptosis and decreased endothelial cell proliferation.

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Acknowledgment

The authors thank Marie-Thérèse Morin, Francoise Mongiat and Calaiselvy Soundaramourty for an excellent technical assistance and Eric Etienne for the help with electronmicroscopy. M.B. was supported by fellowships from the Deutsche Forschungsgemeinschaft (BR 2262/1-1) and the Collège de France.

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Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale Unité 36, Pathologie Vasculaire et Endocrinologie Rénale, Chaire de Médecine Expérimentale, Collège de France, Paris, France

    Marcus Brand, Noël Lamandé, Etienne Larger, Pierre Corvol & Jean-Marie Gasc

  2. Division of Nephrology and Hypertension, Department of Internal Medicine, University of Münster, Münster, Germany

    Marcus Brand

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  1. Marcus Brand
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  2. Noël Lamandé
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  3. Etienne Larger
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  4. Pierre Corvol
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  5. Jean-Marie Gasc
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Correspondence to Jean-Marie Gasc.

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Brand, M., Lamandé, N., Larger, E. et al. Angiotensinogen impairs angiogenesis in the chick chorioallantoic membrane. J Mol Med 85, 451–460 (2007). https://doi.org/10.1007/s00109-006-0141-6

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  • DOI: https://doi.org/10.1007/s00109-006-0141-6

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