Abnormal mechanosensing and cofilin activation promote the progression of ascending aortic aneurysms in mice

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Science Signaling  20 Oct 2015:
Vol. 8, Issue 399, pp. ra105
DOI: 10.1126/scisignal.aab3141

Aberrant mechanosensing and aneurysms

The smooth muscle cells in aortas are connected to the extracellular matrix. Mutations in components of the extracellular matrix, including one called fibulin-4, can weaken the aortic wall, leading to the enlargement of the aortic lumen, a condition known as an aneurysm. Yamashiro et al. found that mice with a smooth muscle cell–specific deficiency in fibulin-4 had disrupted connections between smooth muscle cells and the extracellular matrix, abnormal increases in mechanosensitive proteins, and enhanced activity of an actin cytoskeleton–remodeling enzyme called cofilin. These results suggest that mutations in extracellular matrix components that dispose patients to aneurysms may be due to an inability of the smooth muscle cells to respond appropriately to external mechanical forces. In addition, inhibiting the activity of cofilin or its activating phosphatase SSH1 could prevent the development of aneurysms.

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