Issue |
Med Sci (Paris)
Volume 20, Number 4, Avril 2004
|
|
---|---|---|
Page(s) | 409 - 413 | |
Section | M/S revues | |
DOI | https://doi.org/10.1051/medsci/2004204409 | |
Published online | 15 April 2004 |
Système rénine-angiotensine et remodelage vasculaire
Renin-angiotensin system and vascular remodelling
Inserm U.460, CHU Xavier-Bichat, 16, rue Henri Huchard, 75018 Paris, France
Le système rénine-angiotensine, l’un des principaux complexes de régulation de la pression sanguine, est distribué entre le sang circulant et l’espace péricellulaire de l’interstium tissulaire. Il participe en physiologie et en pathologie de la régulation de la vasomotricité et du remodelage tissulaire dans le système cardiovasculaire. Dans le cadre de ces effets, le système rénine-angiotensine tissulaire agit sur les cellules musculaires lisses vasculaires et les fibroblastes, tandis que le système rénine-angiotensine plasmatique a pour cibles les cellules endothéliales et les leucocytes circulants. L’angiotensine II, peptide actif du système, déclenche différentes voies de signalisation aboutissant à une réponse fonctionnelle immédiate (hypertension artérielle), puis à une réponse structurale hypertrophiante et, enfin, à des réponses pro-inflammatoires et procoagulantes. Dans des modèles expérimentaux d’athérosclérose, la perfusion d’angiotensine II induit la formation d’anévrismes, qui a été reliée à l’activation des leucocytes circulants. Des antagonistes de l’angiotensine II ont, dans ce type de modèle, un effet bénéfique sur le ralentissement de la formation des lesions d’athérosclérose.
Abstract
The renin-angiotensin system (RAS) is compartmented between circulating blood and tissue pericellular space. Whereas renin and its substrate diffuse easily from one compartment to another, the angiotensin peptides act in the compartment where there are generated: blood or pericellular space. Renin is trapped in tissues by low and high affinity receptors. In the target cells, angiotensin II/AT1 receptor interaction generates different signals including an immediate functional calcium-dependent response, secondary hypertrophy and a late proinflammatory and procoagulant response. These late pathological effects are mediated by NADPH oxydase-generated free oxygen radicals and NFκB activation. In vivo, the tissue binding of renin and the induction of converting enzyme are the main determinants of the involvement of the RAS in vascular remodeling. The target cells of interstitial angiotensin II are mainly the vascular smooth muscle cells and fibroblasts, whereas the endothelial cells and circulating leukocytes are the main targets of circulating angiotensin II. In vivo, angiotensin II participates in the vascular wall hypertrophy associated with hypertension. In diabetes, as in other localized fibrotic cardiovascular diseases, the tissue effects of angiotensin II are mainly dependent on its ability to induce TGF-β expression. In experimental atherosclerosis, angiotensin II infusion induces aneurysm formation mediated by activation of circulating leucocytes. In these models, the administration of angiotensin II antagonists has beneficial effects on pathological remodeling. Such beneficial effects of angiotensin II antagonists in localized pathological remodeling have not yet been demonstrated in humans.
© 2004 médecine/sciences - Inserm / SRMS
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