Telomere shortening is a hallmark of genetic cardiomyopathies

Proceedings of the National Academy of Sciences of the United States of America
Alex C Y ChangHelen M Blau

Abstract

This study demonstrates that significantly shortened telomeres are a hallmark of cardiomyocytes (CMs) from individuals with end-stage hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM) as a result of heritable defects in cardiac proteins critical to contractile function. Positioned at the ends of chromosomes, telomeres are DNA repeats that serve as protective caps that shorten with each cell division, a marker of aging. CMs are a known exception in which telomeres remain relatively stable throughout life in healthy individuals. We found that, relative to healthy controls, telomeres are significantly shorter in CMs of genetic HCM and DCM patient tissues harboring pathogenic mutations: TNNI3, MYBPC3, MYH7, DMD, TNNT2, and TTN Quantitative FISH (Q-FISH) of single cells revealed that telomeres were significantly reduced by 26% in HCM and 40% in DCM patient CMs in fixed tissue sections compared with CMs from age- and sex-matched healthy controls. In the cardiac tissues of the same patients, telomere shortening was not evident in vascular smooth muscle cells that do not express or require the contractile proteins, an important control. Telomere shortening was recapitulated in DCM and HCM CMs differentiated from patient...Continue Reading

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Citations

Jan 10, 2019·The Journal of Physiology·Lorenzo R Sewanan, Stuart G Campbell
Feb 12, 2019·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Colleen Jackson-Cook
Jul 25, 2019·Journal of the American Heart Association·Nadya Al-Wakeel-MarquardSabine Klaassen
Feb 10, 2019·The EMBO Journal·Rhys AndersonJoão F Passos
Jun 20, 2020·American Journal of Respiratory Cell and Molecular Biology·Ram P NaikawadiPaul J Wolters
May 3, 2019·The New England Journal of Medicine·Helen M Blau, George Q Daley
May 15, 2020·International Journal of Molecular Sciences·Claudia SacchettoMartina Calore
Feb 23, 2020·Circulation Research·Haobo LiAnthony Rosenzweig
Jan 23, 2021·International Journal of Molecular Sciences·Megan Schmit, Anja-Katrin Bielinsky
Feb 18, 2021·Pflügers Archiv : European journal of physiology·Yong WangShijun Hu
Mar 14, 2021·Nature Communications·Ryan M BaxleyAnja-Katrin Bielinsky
Mar 30, 2021·Oxidative Medicine and Cellular Longevity·Mingjing YanJian Li
Apr 4, 2021·Journal of Clinical Medicine·Ilaria My, Elisa Di Pasquale
Apr 20, 2021·Frontiers in Cell and Developmental Biology·Bin LiAlex C Y Chang
Jan 12, 2022·The FEBS Journal·Mark SweeneyJesús Gil

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Methods Mentioned

BETA
transgenic
FACS
PCR

Software Mentioned

ImageJ

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