Role of a molecular variant of rat atrial natriuretic peptide gene in vascular remodeling

Paola De Paolis, Valerio Nobili, Alessia Lombardi, David Tarasi, Daniela Barbato, Simona Marchitti, Ursula Ganten, Ercole Brunetti, Massimo Volpe, Speranza Rubattu

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)135-140
Number of pages6
JournalAnnals of Clinical and Laboratory Science
Volume37
Issue number2
Publication statusPublished - Mar 2007

Keywords

  • Angiogenesis
  • Atrial natriuretic peptide
  • Endothelial proliferation
  • Gene mutation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Clinical Biochemistry

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