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.
| Original language | English |
|---|---|
| Article number | 9706 |
| Journal | Scientific Reports |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec 1 2017 |
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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, Vol. 7, No. 1, 9706, 01.12.2017.Research output: Contribution to journal › Article
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TY - JOUR
T1 - A rare genetic variant of BPIFB4 predisposes to high blood pressure via impairment of nitric oxide signaling
AU - Vecchione, Carmine
AU - Villa, Francesco
AU - Carrizzo, Albino
AU - Spinelli, Chiara Carmela
AU - Damato, Antonio
AU - Ambrosio, Mariateresa
AU - Ferrario, Anna
AU - Madonna, Michele
AU - Uccellatore, Annachiara
AU - Lupini, Silvia
AU - Maciag, Anna
AU - Ryskalin, Larisa
AU - Milanesi, Luciano
AU - Frati, Giacomo
AU - Sciarretta, Sebastiano
AU - Bellazzi, Riccardo
AU - Genovese, Stefano
AU - Ceriello, Antonio
AU - Auricchio, Alberto
AU - Malovini, Alberto
AU - Puca, Annibale Alessandro
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85028456072&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85028456072&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-10341-x
DO - 10.1038/s41598-017-10341-x
M3 - Article
AN - SCOPUS:85028456072
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 9706
ER -