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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 ANP (C2238/?ANP) on platelet activation in vitro and in human subjects. In vitro, platelets were incubated with no peptide, with T2238/?ANP (WT) or with C2238/?ANP at different concentrations. C2238/?ANP (10^-10 M) induced higher collagen-induced platelet aggregation with respect to both control without ANP and T2238/?ANP. This effect was even stronger at a higher concentration (10^-6 M). Mechanistically, C2238/?ANP significantly lowered platelet cAMP levels, increased ROS production and activated Nox2, with respect to both control and T2238/?ANP. Forskolin, a cAMP activator, and sNOX2-tat, a Nox2 inhibitor, significantly reduced the pro-aggregant effects of C2238/?ANP. 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/?ANP promotes platelet aggregation through the activation of Nox2 and the reduction of cAMP.

SUBMITTER: Carnevale R

PROVIDER: S-EPMC5476672 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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C2238 ANP gene variant promotes increased platelet aggregation through the activation of Nox2 and the reduction of cAMP.

Carnevale Roberto R Pignatelli Pasquale P Frati Giacomo G Nocella Cristina C Stanzione Rosita R Pastori Daniele D Marchitti Simona S Valenti Valentina V Santulli Maria M Barbato Emanuele E Strisciuglio Teresa T Schirone Leonardo L Vecchione Carmine C Violi Francesco F Volpe Massimo M Rubattu Speranza S Sciarretta Sebastiano S

Scientific reports 20170619 1

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<s ...[more]

PMID: 28630469

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Dataset Information

C2238 ANP gene variant promotes increased platelet aggregation through the activation of Nox2 and the reduction of cAMP.

Publications

C2238 ANP gene variant promotes increased platelet aggregation through the activation of Nox2 and the reduction of cAMP.

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