Abstract
Aortic aneurysm is common, accounting for 1–2% of all deaths in industrialized countries. Early theories of the causes of human aneurysm mostly focused on inherited or acquired defects in components of the extracellular matrix in the aorta. Although several mutations in the genes encoding extracellular matrix proteins have been recognized, more recent discoveries have shown important perturbations in cytokine signalling cascades and intracellular components of the smooth muscle contractile apparatus. The modelling of single-gene heritable aneurysm disorders in mice has shown unexpected involvement of the transforming growth factor-β cytokine pathway in aortic aneurysm, highlighting the potential for new therapeutic strategies.
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Acknowledgements
We would like to thank E. Arbustini for the use of the multidetector computer tomographic image in Fig. 1a. We acknowledge funding support from the US National Heart, Lung, and Blood Institute, the Howard Hughes Medical Institute, the US National Marfan Foundation and the William S. Smilow Center for Marfan Research.
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Lindsay, M., Dietz, H. Lessons on the pathogenesis of aneurysm from heritable conditions. Nature 473, 308–316 (2011). https://doi.org/10.1038/nature10145
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