BPIFB4 is associated with exceptional longevity: four single-nucleotide polymorphisms distinguish the wild-type form from a longevity-associated variant conferring positive effects on blood pressure. The effect of a rare variant (RV; allele frequency, 4%) on blood pressure is unknown. Here, we show that overexpression of RV-BPIFB4 in ex-vivo mouse vessels impairs phosphorylation of endothelial nitric oxide synthase (eNOS), blunting acetylcholine-evoked vasorelaxation; in vivo, virally mediated overexpression of RV-BPIFB4 increases blood pressure, an action absent in eNOS-deficient mice. In humans, we found RV carriers to have increased diastolic blood pressure, a finding that was more marked in subjects on anti-hypertensive medication; moreover, recombinant RV-BPIFB4 protein impaired eNOS function in ex-vivo human vessels. Thus, RV-BPIFB4 acts directly on blood pressure homeostasis and may represent a novel biomarker of vascular dysfunction and hypertension.

A rare genetic variant of BPIFB4 predisposes to high blood pressure via impairment of nitric oxide signaling / Vecchione, Carmine; Villa, Francesco; Carrizzo, Albino; Spinelli, Chiara Carmela; Damato, Antonio; Ambrosio, Mariateresa; Ferrario, Anna; Madonna, Michele; Uccellatore, Annachiara; Lupini, Silvia; Maciag, Anna; Ryskalin, Larisa; Milanesi, Luciano; Frati, Giacomo; Sciarretta, Sebastiano; Bellazzi, Riccardo; Genovese, Stefano; Ceriello, Antonio; Auricchio, Alberto; Malovini, Alberto; Puca, Annibale Alessandro. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 7:1(2017). [10.1038/s41598-017-10341-x]

A rare genetic variant of BPIFB4 predisposes to high blood pressure via impairment of nitric oxide signaling

Vecchione, Carmine;Madonna, Michele;Frati, Giacomo;Sciarretta, Sebastiano;
2017

Abstract

BPIFB4 is associated with exceptional longevity: four single-nucleotide polymorphisms distinguish the wild-type form from a longevity-associated variant conferring positive effects on blood pressure. The effect of a rare variant (RV; allele frequency, 4%) on blood pressure is unknown. Here, we show that overexpression of RV-BPIFB4 in ex-vivo mouse vessels impairs phosphorylation of endothelial nitric oxide synthase (eNOS), blunting acetylcholine-evoked vasorelaxation; in vivo, virally mediated overexpression of RV-BPIFB4 increases blood pressure, an action absent in eNOS-deficient mice. In humans, we found RV carriers to have increased diastolic blood pressure, a finding that was more marked in subjects on anti-hypertensive medication; moreover, recombinant RV-BPIFB4 protein impaired eNOS function in ex-vivo human vessels. Thus, RV-BPIFB4 acts directly on blood pressure homeostasis and may represent a novel biomarker of vascular dysfunction and hypertension.
2017
multidisciplinary
01 Pubblicazione su rivista::01a Articolo in rivista
A rare genetic variant of BPIFB4 predisposes to high blood pressure via impairment of nitric oxide signaling / Vecchione, Carmine; Villa, Francesco; Carrizzo, Albino; Spinelli, Chiara Carmela; Damato, Antonio; Ambrosio, Mariateresa; Ferrario, Anna; Madonna, Michele; Uccellatore, Annachiara; Lupini, Silvia; Maciag, Anna; Ryskalin, Larisa; Milanesi, Luciano; Frati, Giacomo; Sciarretta, Sebastiano; Bellazzi, Riccardo; Genovese, Stefano; Ceriello, Antonio; Auricchio, Alberto; Malovini, Alberto; Puca, Annibale Alessandro. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 7:1(2017). [10.1038/s41598-017-10341-x]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1079270
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