Mechanical stretch-induced endoplasmic reticulum stress, apoptosis and inflammation contribute to thoracic aortic aneurysm and dissection

The Journal of Pathology
Li-Xin JiaJie Du

Abstract

Thoracic aortic aneurysm/dissection (TAAD) is characterized by excessive smooth muscle cell (SMC) loss, extracellular matrix (ECM) degradation and inflammation. In response to certain stimuli, endoplasmic reticulum (ER) stress is activated and regulates apoptosis and inflammation. Excessive apoptosis promotes aortic inflammation and degeneration, leading to TAAD. Therefore, we studied the role of ER stress in TAAD formation. A lysyl oxidase inhibitor, 3-aminopropionitrile fumarate (BAPN), was administrated to induce TAAD formation in mice, which showed significant SMC loss (α-SMA level). Excessive apoptosis (TUNEL staining) and ER stress (ATF4 and CHOP), along with inflammation, were present in TAAD samples from both mouse and human. Transcriptional profiling of SMCs after mechanical stress demonstrated the expression of genes for ER stress and inflammation. To explore the causal role of ER stress in initiating degenerative signalling events and TAAD, we treated wild-type (CHOP(+/+)) or CHOP(-/-) mice with BAPN and found that CHOP deficiency protected against TAAD formation and rupture, as well as reduction in α-SMA level. Both SMC apoptosis and inflammation were significantly reduced in CHOP(-/-) mice. Moreover, SMCs isolated ...Continue Reading

References

Feb 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·A J ManiotisD E Ingber
May 20, 1998·The American Journal of Clinical Nutrition·R B RuckerC L Keen
Jul 9, 2002·Apoptosis : an International Journal on Programmed Cell Death·Seiichi OyadomariM Mori
Dec 20, 2003·Cell Death and Differentiation·S Oyadomari, M Mori
Feb 16, 2005·Circulation·Eric M Isselbacher
Oct 4, 2005·The Journal of Clinical Investigation·Chunyan XuJohn C Reed
Sep 6, 2006·EMBO Reports·Eva SzegezdiAfshin Samali
Jun 15, 2007·Nature Reviews. Molecular Cell Biology·David Ron, Peter Walter
Apr 29, 2008·Current Problems in Cardiology·John A Elefteriades
Mar 24, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Nicholas J LeeperThomas Quertermous
Jun 23, 2009·Cardiovascular Research·Susanne W M van den BorneW Matthijs Blankesteijn
Nov 4, 2009·Nature Reviews. Cardiology·Ismail El-Hamamsy, Magdi H Yacoub
Nov 17, 2009·Journal of Molecular and Cellular Cardiology·Tetsuo Minamino, Masafumi Kitakaze
Jul 10, 2010·Circulation Research·Masafumi Kitakaze, Osamu Tsukamoto
Oct 30, 2010·Circulation Research·Tetsuo MinaminoMasafumi Kitakaze
May 20, 2011·Nature·Mark E Lindsay, Harry C Dietz
Nov 9, 2012·Circulation·Tomohiro KuriharaYasunori Okada
Mar 29, 2013·The Journal of Thoracic and Cardiovascular Surgery·Hirotsugu KurobeTetsuya Kitagawa
Jul 17, 2013·The Journal of Surgical Research·Darrell WuScott A LeMaire

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Citations

Nov 8, 2015·Biochemical and Biophysical Research Communications·Zhuoli ZhuHaiyang Yu
Jul 28, 2018·Cardiovascular Research·Juliette RaffortZiad Mallat
Jul 21, 2017·Journal of the American Heart Association·Lixin JiaJie Du
Jun 29, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Allan R Brasier
Sep 16, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Fabien LareyreZiad Mallat
Feb 4, 2016·Circulation Research·Dong-chuan GuoDianna M Milewicz
Sep 8, 2018·Experimental Physiology·Shanshan WangJingang Zheng
Jan 24, 2019·Annals of Biomedical Engineering·Md Tausif SalimAjit P Yoganathan
Feb 26, 2019·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Amalia ForteAlessandro Della Corte
Apr 26, 2019·Journal of Cellular and Molecular Medicine·Bin FangQingfeng Li
Jul 17, 2019·Apoptosis : an International Journal on Programmed Cell Death·Juan Ignacio BurgosMartin Vila Petroff
Feb 23, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Bo LiuZamaneh Kassiri
Apr 24, 2020·Journal of Cardiovascular Pharmacology and Therapeutics·Sheng LeJiahong Xia
May 13, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tsz Wing YimJoyce Cheung-Flynn
Aug 12, 2020·Journal of Cell Communication and Signaling·Jingbo ChenChaohong Li
Aug 5, 2020·Journal of Zhejiang University. Science. B·Hai-Qiong ZhengJian-An Wang
Jun 22, 2020·Cardiovascular Drugs and Therapy·Fang WangJingang Zheng
Sep 28, 2018·Mediators of Inflammation·Jing YeYingzhong Lin
May 31, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Ploingarm PetsophonsakulLeon Schurgers
Apr 24, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yoshito YamashiroHiromi Yanagisawa
Apr 9, 2020·Frontiers in Bioengineering and Biotechnology·Fengxuan HanBin Li
Aug 25, 2020·Translational Research : the Journal of Laboratory and Clinical Medicine·Jiyuan PiaoYoungsook Son
Feb 27, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Brittany O AicherAreck A Ucuzian

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Methods Mentioned

BETA
dissection
fluorescence microscopy
dissections
flow cytometry

Software Mentioned

ImageProPlus

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