Role of a molecular variant of rat atrial natriuretic Peptide gene in vascular remodeling.
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.
De Paolis
Paola
P
Research Center, San Pietro Hospital, Rome, Italy.
Nobili
Valerio
V
Lombardi
Alessia
A
Tarasi
David
D
Barbato
Daniela
D
Marchitti
Simona
S
Ganten
Ursula
U
Brunetti
Ercole
E
Volpe
Massimo
M
Rubattu
Speranza
S
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
D017077:Culture Media, Conditioned; C472610:atrial natriuretic peptide, rat; D009320:Atrial Natriuretic Factor