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(Hypertension. 2002;39:224.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Angiotensinogen and Its Cleaved Derivatives Inhibit Angiogenesis

Jérôme Célérier; Amauri Cruz; Noël Lamandé; Jean-Marie Gasc; Pierre Corvol

From the 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.

Correspondence to Dr Pierre Corvol, INSERM U36–Collège de France, 11, place Marcelin Berthelot, 75231 Paris Cedex 05, France. E-mail pierre.corvol{at}college-de-france.fr

The members of the serine protease inhibitor (serpin) family, which share a common tertiary structure and a role as serin protease inhibitors, are involved in a variety of newly discovered functions. For example, antithrombin III exerts a strong antiangiogenic activity. Angiotensinogen, the renin substrate, has a folded structure and is a member of the noninhibitory serpin subfamily. Two other noninhibitory serpins, maspin and pigment epithelium-derived factor, have antiangiogenic properties. We investigated the antiangiogenic effect of angiotensinogen and 2 related compounds: (1) des(angiotensin I)angiotensinogen, the product of angiotensinogen cleavage by renin, and (2) the reactive center loop-cleaved angiotensinogen, which is produced after selective and limited proteolysis by the protease V8. We used well-established in vitro (endothelial cell proliferation and migration, and capillary-like tube formation on Matrigel) and in vivo (the chick chorioallantoic membrane assay) models of angiogenesis to evaluate the antiangiogenic activities of these 3 related molecules. Our data demonstrated that these compounds exerted a clear and equipotent antiangiogenic effect, thus attributing a novel function to angiotensinogen and des(angiotensin I)angiotensinogen, for which no function was previously known.

Key Words: angiotensinogen • angiotensin I • endothelial growth factors

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