Previous studies in a hypertensive animal model of stroke and in humans showed that mutations of the atrial natriuretic peptide (ANP) gene are associated with increased risk of stroke. To elucidate the vascular disease mechanisms that result from structural modifications of the ANP gene, we investigated a coding mutation of the ANP gene in stroke-prone spontaneously hypertensive rats (SHRsp). This mutation leads to a Gly/Ser transposition in the prosegment of ANP. We found that presence of this mutation is associated with increased immunostaining of ANP in the wall of SHRsp cerebral vessels. The mutation causes a major inhibitory effect on endothelial cell proliferation, as assessed by thymidine incorporation, and on angiogenesis, as determined by an endothelial cell tube formation assay, in human umbilical vein endothelial cells (HUVEC) exposed to ANP/SHRsp. These in vitro findings show that the SHRsp-derived form of ANP has an inhibitory effect on vascular remodeling and they provide further support for a role of the ANP gene in the pathogenesis of cerebrovascular disease in the animal model.

Role of a molecular variant of the rat atrial natriuretic peptide gene on vascular remodeling / DE PAOLIS, P; V., Nobili; Lombardi, A; Tarasi, D; Barbato, D; Marchitti, S; Ganten, U; Brunetti, E; Volpe, Massimo; Rubattu, Speranza Donatella. - In: ANNALS OF CLINICAL AND LABORATORY SCIENCE. - ISSN 0091-7370. - 37:(2007), pp. 135-140.

Role of a molecular variant of the rat atrial natriuretic peptide gene on vascular remodeling.

VOLPE, Massimo;RUBATTU, Speranza Donatella
2007

Abstract

Previous studies in a hypertensive animal model of stroke and in humans showed that mutations of the atrial natriuretic peptide (ANP) gene are associated with increased risk of stroke. To elucidate the vascular disease mechanisms that result from structural modifications of the ANP gene, we investigated a coding mutation of the ANP gene in stroke-prone spontaneously hypertensive rats (SHRsp). This mutation leads to a Gly/Ser transposition in the prosegment of ANP. We found that presence of this mutation is associated with increased immunostaining of ANP in the wall of SHRsp cerebral vessels. The mutation causes a major inhibitory effect on endothelial cell proliferation, as assessed by thymidine incorporation, and on angiogenesis, as determined by an endothelial cell tube formation assay, in human umbilical vein endothelial cells (HUVEC) exposed to ANP/SHRsp. These in vitro findings show that the SHRsp-derived form of ANP has an inhibitory effect on vascular remodeling and they provide further support for a role of the ANP gene in the pathogenesis of cerebrovascular disease in the animal model.
2007
01 Pubblicazione su rivista::01a Articolo in rivista
Role of a molecular variant of the rat atrial natriuretic peptide gene on vascular remodeling / DE PAOLIS, P; V., Nobili; Lombardi, A; Tarasi, D; Barbato, D; Marchitti, S; Ganten, U; Brunetti, E; Volpe, Massimo; Rubattu, Speranza Donatella. - In: ANNALS OF CLINICAL AND LABORATORY SCIENCE. - ISSN 0091-7370. - 37:(2007), pp. 135-140.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/366804
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