Williams syndrome predisposes to vascular stiffness modified by antihypertensive use and copy number changes in NCF1
Williams syndrome is caused by the deletion of 26 to 28 genes, including elastin, on human chromosome 7. Elastin insufficiency leads to the cardiovascular hallmarks of this condition, namely focal stenosis and hypertension. Extrapolation from the Eln(+/-) mouse suggests that affected people may also have stiff vasculature, a risk factor for stroke, myocardial infarction, and cardiac death. NCF1, one of the variably deleted Williams genes, is a component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex and is involved in the generation of oxidative stress, making it an interesting candidate modifier for vascular stiffness. Using a case-control design, vascular stiffness was evaluated by pulse wave velocity in 77 Williams cases and matched controls. Cases had stiffer conducting vessels than controls (P<0.001), with increased stiffness observed in even the youngest children with Williams syndrome. Pulse wave velocity increased with age at comparable rates in cases and controls, and although the degree of vascular stiffness varied, it was seen in both hypertensive and normotensive Williams participants. Use of antihypertensive medication and extension of the Williams deletion to include NCF1 were associated with protection from vascular stiffness. These findings demonstrate that vascular stiffness is a primary vascular phenotype in Williams syndrome and that treatment with antihypertensives or agents inhibiting oxidative stress may be important in managing patients with this condition, potentially even those who are not overtly hypertensive.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2014 |
|---|---|
| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:63 |
|---|---|
| Enthalten in: |
Hypertension (Dallas, Tex. : 1979) - 63(2014), 1 vom: 01. Jan., Seite 74-9 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kozel, Beth A [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 11.04.2014 Date Revised 15.11.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1161/HYPERTENSIONAHA.113.02087 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM231704658 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM231704658 | ||
| 003 | DE-627 | ||
| 005 | 20231224091348.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2014 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1161/HYPERTENSIONAHA.113.02087 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0772.xml |
| 035 | |a (DE-627)NLM231704658 | ||
| 035 | |a (NLM)24126171 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kozel, Beth A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Williams syndrome predisposes to vascular stiffness modified by antihypertensive use and copy number changes in NCF1 |
| 264 | 1 | |c 2014 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 11.04.2014 | ||
| 500 | |a Date Revised 15.11.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Williams syndrome is caused by the deletion of 26 to 28 genes, including elastin, on human chromosome 7. Elastin insufficiency leads to the cardiovascular hallmarks of this condition, namely focal stenosis and hypertension. Extrapolation from the Eln(+/-) mouse suggests that affected people may also have stiff vasculature, a risk factor for stroke, myocardial infarction, and cardiac death. NCF1, one of the variably deleted Williams genes, is a component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex and is involved in the generation of oxidative stress, making it an interesting candidate modifier for vascular stiffness. Using a case-control design, vascular stiffness was evaluated by pulse wave velocity in 77 Williams cases and matched controls. Cases had stiffer conducting vessels than controls (P<0.001), with increased stiffness observed in even the youngest children with Williams syndrome. Pulse wave velocity increased with age at comparable rates in cases and controls, and although the degree of vascular stiffness varied, it was seen in both hypertensive and normotensive Williams participants. Use of antihypertensive medication and extension of the Williams deletion to include NCF1 were associated with protection from vascular stiffness. These findings demonstrate that vascular stiffness is a primary vascular phenotype in Williams syndrome and that treatment with antihypertensives or agents inhibiting oxidative stress may be important in managing patients with this condition, potentially even those who are not overtly hypertensive | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a NADPH oxidase | |
| 650 | 4 | |a Williams syndrome | |
| 650 | 4 | |a elastin | |
| 650 | 4 | |a pulse wave analysis | |
| 650 | 4 | |a vascular stiffness | |
| 650 | 7 | |a Antihypertensive Agents |2 NLM | |
| 650 | 7 | |a NADPH Oxidases |2 NLM | |
| 650 | 7 | |a EC 1.6.3.- |2 NLM | |
| 650 | 7 | |a neutrophil cytosolic factor 1 |2 NLM | |
| 650 | 7 | |a EC 1.6.3.1 |2 NLM | |
| 700 | 1 | |a Danback, Joshua R |e verfasserin |4 aut | |
| 700 | 1 | |a Waxler, Jessica L |e verfasserin |4 aut | |
| 700 | 1 | |a Knutsen, Russell H |e verfasserin |4 aut | |
| 700 | 1 | |a de Las Fuentes, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Reusz, Gyorgy S |e verfasserin |4 aut | |
| 700 | 1 | |a Kis, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Bhatt, Ami B |e verfasserin |4 aut | |
| 700 | 1 | |a Pober, Barbara R |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Hypertension (Dallas, Tex. : 1979) |d 1983 |g 63(2014), 1 vom: 01. Jan., Seite 74-9 |w (DE-627)NLM000456136 |x 1524-4563 |7 nnns |
| 773 | 1 | 8 | |g volume:63 |g year:2014 |g number:1 |g day:01 |g month:01 |g pages:74-9 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.02087 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 63 |j 2014 |e 1 |b 01 |c 01 |h 74-9 | ||