Williams syndrome predisposes to vascular stiffness modified by antihypertensive use and copy number changes in NCF1

Beth A. Kozel, Joshua R. Danback, Jessica L. Waxler, Russell H. Knutsen, Lisa De Las Fuentes, Gyorgy S. Reusz, Eva Kis, Ami B. Bhatt, Barbara R. Pober

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


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.

Original languageEnglish
Pages (from-to)74-79
Number of pages6
Issue number1
StatePublished - Jan 2014


  • Elastin
  • NADPH oxidase
  • Pulse wave analysis
  • Vascular stiffness
  • Williams syndrome


Dive into the research topics of 'Williams syndrome predisposes to vascular stiffness modified by antihypertensive use and copy number changes in NCF1'. Together they form a unique fingerprint.

Cite this