title: Role of a molecular variant of rat atrial natriuretic Peptide gene in vascular remodeling.
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.
authors.affiliation: Research Center, San Pietro Hospital, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: De Paolis
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
authors.forename: Alessia
authors.initials: A
authors.lastname: Lombardi
authors.forename: David
authors.initials: D
authors.lastname: Tarasi
authors.forename: Daniela
authors.initials: D
authors.lastname: Barbato
authors.forename: Simona
authors.initials: S
authors.lastname: Marchitti
authors.forename: Ursula
authors.initials: U
authors.lastname: Ganten
authors.forename: Ercole
authors.initials: E
authors.lastname: Brunetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
authors.forename: Speranza
authors.initials: S
authors.lastname: Rubattu
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000098:blood supply*; D009154:Mutation; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000235:genetics*; D014162:Transfection; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D017077:Culture Media, Conditioned; C472610:atrial natriuretic peptide, rat; D009320:Atrial Natriuretic Factor