Skip to main content

Understanding the Role of Oxidative Stress in Altering Cardiovascular Disease Severity in Williams Syndrome. A. Troia, R. Knutsen, J. Danback, B. Kozel; Laboratory of Vascular and Matrix Genetics

Thursday, September 14, 2017 — Poster Session III

12:00 p.m. – 1:30 p.m.
FAES Terrace


  • A Troia
  • R Knutsen
  • J Danback
  • B Kozel


Williams syndrome (WS) is caused by the deletion of 26-28 genes, including elastin, on chromosome 7. Elastin insufficiency leads to the cardiovascular hallmarks of this condition, including hypertension and vascular stiffness. Previous studies in WS patients showed that longer deletions that also included the NCF1 gene were associated with lower blood pressure and vascular stiffness. NCF1 is a component of Nox1 and Nox2 NADPH oxidase complexes that generate reactive oxygen species (ROS). Nox1 and Nox2 are expressed in different areas of the vascular wall and vary in ROS generating activity. DHE/HPLC assays on mouse aortas confirmed that Eln+/-‘ s had greater superoxide levels than Eln WTs. To analyze the Nox effect on elastin insufficiency, we crossed Eln+/- to Ncf1+/-, Nox1-/y, or Nox2-/y mice. Ncf1 insuffiency improved cardiovascular conditions in Eln+/-, but not WT mice. Moreover, chornic administration of apocynin, a general Nox inhibitor, also decreased blood pressure in the Eln+/-, whereas the drug had limited impact on the Eln WT. These findings suggest that oxidative stress plays an important role in the generation of hypertension and vascular stiffness (secondarily) in Eln+/- mice. When assessing the role of each specific Nox complex, it was found that decreased Nox1 produced lowered blood pressure and improved functional stiffness of the conducting vessels of Eln+/- mice. Analysis of Nox2 data is currently still underway. Evaluation of large vessel histology revealed no changes in lamellar structure or function. Consequently, future work will focus on understanding how oxidative stress impacts smaller resistance vessels.

Category: Molecular Biology and Biochemistry