Role of rat α adducin in angiogenesis: Null effect of the F316Y polymorphism

Claudia Cappuzzello, Roberta Melchionna, Antonella Mangoni, Grazia Tripodi, Patrizia Ferrari, Lucia Torielli, Diego Arcelli, Mauro Helmer-Citterich, Giuseppe Bianchi, Maurizio C. Capogrossi, Monica Napolitano

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Rat α adducin point mutation (F316Y) has been associated with primary systemic arterial hypertension. As microcirculatory abnormalities are present in most forms of hypertension, the aim of the present study was to investigate whether rat α adducin may regulate endothelial cell (EC) functions in vitro and in vivo. Methods and results: The overexpression of rat wild type α adducin (WT-Add1) in ECs induced capillary-like structure development in Matrigel in vitro and enhanced capillary formation in Matrigel implants in vivo in CD1 mice. In contrast, the overexpression of the mutated form (MUT-Add1) of rat α adducin had a Null effect in vitro and lacked any significant activity in vivo. Further, adenovirus-mediated rat WT-Add1 but not MUT-Add1 gene transfer to murine ischemic hindlimb enhanced capillary formation in skeletal muscles. Gene profiling of human umbilical vein endothelial cells overexpressing α adducin was performed in order to identify putative effector molecules of α adducin-mediated activities on ECs. Interestingly, among a number of genes involved in angiogenesis regulation, retinoic acid-induced protein (RAI17) was found to be upregulated in WT-Add1 vs MUT-Add1 overexpressing cells, possibly representing a key molecule/axis for the functional Add1-induced effect. Conclusions: Rat WT α adducin enhanced EC functions both in vitro and in vivo. The expression of the F316Y variant, associated with the hypertensive phenotype, had a Null effect and might contribute to endothelial rarefaction/dysfunction in hypertension. RAI17 was found to be a putative effector molecule differentially regulated by the overexpression of the two forms of Add1 in endothelial cells.

Original languageEnglish
Pages (from-to)608-617
Number of pages10
JournalCardiovascular Research
Volume75
Issue number3
DOIs
Publication statusPublished - Aug 1 2007

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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