Angiotensinogen modulates renal vasculature growth.
We have shown previously that angiotensinogen, like other members of the serine protease inhibitor family, has antiangiogenic properties in vitro on cultured endothelial cells and in ovo in the chick chorioallantoic membrane assay. The aim of this study was to show the effects of angiotensinogen on vascular wall remodeling in vivo. We measured the vessel wall thickness (tunica media) stained with an antibody to alpha-actin. In the kidney, arterioles were 21.5% thinner in male transgenic mice overexpressing human angiotensinogen than in male control animals. In other vascular beds, the arterial wall thickness was not affected. By using in situ hybridization and Northern blot analysis, human angiotensinogen expression was detected at a high level in the male kidney and at a much lower level in other organs. There is a relationship between the effect of angiotensinogen on arterial wall thickness and the local expression level of angiotensinogen in this model of transgenic mice. Because human angiotensinogen is not cleaved to a significant extent by mouse renin, the reduction in kidney arterial wall thickness is because of angiotensinogen itself and not angiotensin II, and we show that the reduction was not because of hypoplasia or hypotropia. In contrast, a marked difference in the expression of platelet-derived growth factor receptor-beta was observed in the kidney arterioles at day 5 when compared with controls. Altogether, these observations provide the first quantitative evidence that a high level of angiotensinogen expression can inhibit the growth of kidney artery walls in vivo.
Brand
Marcus
M
Institut National de la Santé et de la Recherche Médicale Unité 36, Pathologie Vasculaire et Endocrinologie Rénale, Collège de France, Paris, France.
Lamandé
Noël
N
Sigmund
Curt D
CD
Larger
Etienne
E
Corvol
Pierre
P
Gasc
Jean-Marie
JM
D000808:Angiotensinogen / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001808:Blood Vessels / Q000254:growth & development / Q000502:physiology; D002452:Cell Count; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D012077:Renal Artery / Q000033:anatomy & histology; D014018:Tissue Distribution
D012333:RNA, Messenger; D000808:Angiotensinogen