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

Abstract

Hutchinson-Gilford progeria syndrome is a disorder of premature aging in children caused by de novo mutations in LMNA that lead to the synthesis of an internally truncated form of prelamin A (commonly called progerin). The production of progerin causes multiple disease phenotypes, including an unusual vascular phenotype characterized by the loss of smooth muscle cells in the arterial media and fibrosis of the adventitia. We show that progerin expression, combined with mechanical stress, promotes smooth muscle cell death. Disrupting the linker of the nucleoskeleton and cytoskeleton (LINC) complex in smooth muscle cells ameliorates the toxic effects of progerin on smooth muscle cells and limits the accompanying adventitial fibrosis.

• Authors: Paul H Kim, Jennings Luu, Patrick Heizer, Yiping Tu, Thomas A Weston, Natalie Chen, Christopher Lim, Robert L Li, Po-Yu Lin, James C Y Dunn, Didier Hodzic, Stephen G Young, Loren G Fong
• Journal: Science translational medicine (Sci Transl Med) Vol. 10 Issue 460 (09 26 2018) ISSN: 1946-6242 [Electronic] United States
• PMID: 30257952 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Chemical References

• Collagen Type VIII
• Lamin Type A
• Lamin Type B
• Multiprotein Complexes
• prelamin A

Topics

• Adventitia (metabolism, pathology)
• Animals
• Aorta (metabolism, pathology)
• Aortic Diseases (complications)
• Cell Death
• Cells, Cultured
• Collagen Type VIII (biosynthesis)
• Disease Models, Animal
• Lamin Type A (metabolism)
• Lamin Type B (metabolism)
• Mice
• Multiprotein Complexes (metabolism)
• Myocytes, Smooth Muscle (metabolism, ultrastructure)
• Phenotype
• Progeria (complications, metabolism)