Publications · Science Translational Medicine 2018 · First author

Disrupting the LINC complex in smooth muscle cells reduces aortic disease in a mouse model of Hutchinson-Gilford progeria syndrome

Showed that reducing force transmission to the nucleus protects smooth muscle cells and ameliorates arterial disease.

The question

Children with progeria lose the smooth muscle cells in their artery walls, and the outer layer of the artery scars. Is mechanical force reaching the nucleus part of the problem?

What we found

• Progerin combined with mechanical stress kills smooth muscle cells.
• The LINC complex links the cytoskeleton to the nucleus and carries force onto it. Disrupting it in smooth muscle cells reduced the toxic effects of progerin.
• It also limited the scarring (adventitial fibrosis) of the aorta in progeria mice.

Why it matters

It showed that shielding the nucleus from mechanical force can protect the arteries in a model of progeria. The paper was featured on the cover of Science Translational Medicine.

Disrupting the LINC complex in smooth muscle cells reduces aortic disease in a mouse model of Hutchinson-Gilford progeria syndrome. Science Translational Medicine (2018). doi:10.1126/scitranslmed.aat7163