C2238 ANP gene variant promotes increased platelet aggregation through the activation of Nox2 and the reduction of cAMP
Abstract Subjects carrying the C2238 variant of the atrial natriuretic peptide (ANP) gene have a higher occurrence of stroke and acute coronary syndrome, suggesting an increased predisposition to acute thrombotic events in these subjects. We evaluated for the first time the direct effects of mutant...
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Nature Portfolio
2017
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oai:doaj.org-article:5096f14f92b54f8a9f71e3827294a48d2021-12-02T12:31:50ZC2238 ANP gene variant promotes increased platelet aggregation through the activation of Nox2 and the reduction of cAMP10.1038/s41598-017-03679-92045-2322https://doaj.org/article/5096f14f92b54f8a9f71e3827294a48d2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03679-9https://doaj.org/toc/2045-2322Abstract Subjects carrying the C2238 variant of the atrial natriuretic peptide (ANP) gene have a higher occurrence of stroke and acute coronary syndrome, suggesting an increased predisposition to acute thrombotic events in these subjects. We evaluated for the first time the direct effects of mutant ANP (C2238/αANP) on platelet activation in vitro and in human subjects. In vitro, platelets were incubated with no peptide, with T2238/αANP (WT) or with C2238/αANP at different concentrations. C2238/αANP (10−10 M) induced higher collagen-induced platelet aggregation with respect to both control without ANP and T2238/αANP. This effect was even stronger at a higher concentration (10−6 M). Mechanistically, C2238/αANP significantly lowered platelet cAMP levels, increased ROS production and activated Nox2, with respect to both control and T2238/αANP. Forskolin, a cAMP activator, and sNOX2-tat, a Nox2 inhibitor, significantly reduced the pro-aggregant effects of C2238/αANP. In vivo, we found that platelet aggregation resulted to be higher in patients with atrial fibrillation carrying the C2238 ANP gene variant with respect to non-carriers. In conclusions, C2238/αANP promotes platelet aggregation through the activation of Nox2 and the reduction of cAMP.Roberto CarnevalePasquale PignatelliGiacomo FratiCristina NocellaRosita StanzioneDaniele PastoriSimona MarchittiValentina ValentiMaria SantulliEmanuele BarbatoTeresa StrisciuglioLeonardo SchironeCarmine VecchioneFrancesco VioliMassimo VolpeSperanza RubattuSebastiano SciarrettaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) |
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DOAJ |
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Medicine R Science Q |
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Medicine R Science Q Roberto Carnevale Pasquale Pignatelli Giacomo Frati Cristina Nocella Rosita Stanzione Daniele Pastori Simona Marchitti Valentina Valenti Maria Santulli Emanuele Barbato Teresa Strisciuglio Leonardo Schirone Carmine Vecchione Francesco Violi Massimo Volpe Speranza Rubattu Sebastiano Sciarretta C2238 ANP gene variant promotes increased platelet aggregation through the activation of Nox2 and the reduction of cAMP |
| description |
Abstract Subjects carrying the C2238 variant of the atrial natriuretic peptide (ANP) gene have a higher occurrence of stroke and acute coronary syndrome, suggesting an increased predisposition to acute thrombotic events in these subjects. We evaluated for the first time the direct effects of mutant ANP (C2238/αANP) on platelet activation in vitro and in human subjects. In vitro, platelets were incubated with no peptide, with T2238/αANP (WT) or with C2238/αANP at different concentrations. C2238/αANP (10−10 M) induced higher collagen-induced platelet aggregation with respect to both control without ANP and T2238/αANP. This effect was even stronger at a higher concentration (10−6 M). Mechanistically, C2238/αANP significantly lowered platelet cAMP levels, increased ROS production and activated Nox2, with respect to both control and T2238/αANP. Forskolin, a cAMP activator, and sNOX2-tat, a Nox2 inhibitor, significantly reduced the pro-aggregant effects of C2238/αANP. In vivo, we found that platelet aggregation resulted to be higher in patients with atrial fibrillation carrying the C2238 ANP gene variant with respect to non-carriers. In conclusions, C2238/αANP promotes platelet aggregation through the activation of Nox2 and the reduction of cAMP. |
| format |
article |
| author |
Roberto Carnevale Pasquale Pignatelli Giacomo Frati Cristina Nocella Rosita Stanzione Daniele Pastori Simona Marchitti Valentina Valenti Maria Santulli Emanuele Barbato Teresa Strisciuglio Leonardo Schirone Carmine Vecchione Francesco Violi Massimo Volpe Speranza Rubattu Sebastiano Sciarretta |
| author_facet |
Roberto Carnevale Pasquale Pignatelli Giacomo Frati Cristina Nocella Rosita Stanzione Daniele Pastori Simona Marchitti Valentina Valenti Maria Santulli Emanuele Barbato Teresa Strisciuglio Leonardo Schirone Carmine Vecchione Francesco Violi Massimo Volpe Speranza Rubattu Sebastiano Sciarretta |
| author_sort |
Roberto Carnevale |
| title |
C2238 ANP gene variant promotes increased platelet aggregation through the activation of Nox2 and the reduction of cAMP |
| title_short |
C2238 ANP gene variant promotes increased platelet aggregation through the activation of Nox2 and the reduction of cAMP |
| title_full |
C2238 ANP gene variant promotes increased platelet aggregation through the activation of Nox2 and the reduction of cAMP |
| title_fullStr |
C2238 ANP gene variant promotes increased platelet aggregation through the activation of Nox2 and the reduction of cAMP |
| title_full_unstemmed |
C2238 ANP gene variant promotes increased platelet aggregation through the activation of Nox2 and the reduction of cAMP |
| title_sort |
c2238 anp gene variant promotes increased platelet aggregation through the activation of nox2 and the reduction of camp |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/5096f14f92b54f8a9f71e3827294a48d |
| work_keys_str_mv |
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