Disrupting the LINC Complex in Smooth Muscle Cells Reduces Aortic Disease in a Mouse Model of Hutchinson-Gilford Progeria Syndrome

Overview

Journal Sci Transl Med

Specialties General Medicine
Science

Date 2018 Sep 28

PMID 30257952

Citations 47

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

Affiliations

Soon will be listed here.

Abstract

Hutchinson-Gilford progeria syndrome is a disorder of premature aging in children caused by de novo mutations in 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.

Citing Articles

The Accumulation of Progerin Underlies the Loss of Aortic Smooth Muscle Cells in Hutchinson-Gilford Progeria Syndrome.

Kim P, Kim J, Heizer P, Jung H, Tu Y, Presnell A bioRxiv. 2024; .

PMID: 39554077 PMC: 11565845. DOI: 10.1101/2024.10.29.620896.

Mechanotransduction of the vasculature in Hutchinson-Gilford Progeria Syndrome.

Shores K, Truskey G Front Physiol. 2024; 15:1464678.

PMID: 39239311 PMC: 11374724. DOI: 10.3389/fphys.2024.1464678.

Cardiac and skeletal muscle manifestations in the G608G mouse model of Hutchinson-Gilford progeria syndrome.

Hong Y, Rannou A, Manriquez N, Antich J, Liu W, Fournier M Aging Cell. 2024; 23(10):e14259.

PMID: 38961628 PMC: 11464102. DOI: 10.1111/acel.14259.

Progerin forms an abnormal meshwork and has a dominant-negative effect on the nuclear lamina.

Kim P, Kim J, Tu Y, Jung H, Jeong J, Tran A Proc Natl Acad Sci U S A. 2024; 121(27):e2406946121.

PMID: 38917015 PMC: 11228511. DOI: 10.1073/pnas.2406946121.

Long lifetime and tissue-specific accumulation of lamin A/C in Hutchinson-Gilford progeria syndrome.

Hasper J, Welle K, Swovick K, Hryhorenko J, Ghaemmaghami S, Buchwalter A J Cell Biol. 2023; 223(1).

PMID: 37966721 PMC: 10651395. DOI: 10.1083/jcb.202307049.

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