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Annals of Clinical & Laboratory Science 37:135-140 (2007)
© 2007 Association of Clinical Scientists

Role of a Molecular Variant of Rat Atrial Natriuretic Peptide Gene in Vascular Remodeling

Paola De Paolisa,b, Valerio Nobilia, Alessia Lombardic, David Tarasib, Daniela Barbatoc, Simona Marchittic, Ursula Gantend, Ercole Brunettia, Massimo Volpeb,c and Speranza Rubattub,c
a Research Center, San Pietro Hospital, Rome; b Cardiology Department, IInd School of Medicine, La Sapienza University, Saint Andrea Hospital, Rome; c IRCCS Neuromed, Pozzilli, Italy; and d MDC, Center for Molecular Medicine, Berlin, Germany.

Address correspondence to Speranza Rubattu, M.D., IRCCS Neuromed, Localita’ Camerelle, 86077 Pozzilli (Isernia), Italy; tel 0039 0865 915227; fax 0039 0865 927575; e-mail: rubattu.speranza{at}neuromed.it.

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.

Keywords: atrial natriuretic peptide, gene mutation, endothelial proliferation, angiogenesis






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