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In response to certain stimuli, endoplasmic reticulum (ER<\/jats:styled-content>) stress is activated and regulates apoptosis and inflammation. Excessive apoptosis promotes aortic inflammation and degeneration, leading to TAAD<\/jats:styled-content>. Therefore, we studied the role of ER<\/jats:styled-content> stress in TAAD<\/jats:styled-content> formation. A lysyl oxidase inhibitor, 3\u2010aminopropionitrile fumarate (BAPN<\/jats:styled-content>), was administrated to induce TAAD<\/jats:styled-content> formation in mice, which showed significant SMC<\/jats:styled-content> loss (\u03b1\u2010SMA<\/jats:styled-content> level). Excessive apoptosis (TUNEL<\/jats:styled-content> staining) and ER<\/jats:styled-content> stress (ATF4<\/jats:styled-content> and CHOP<\/jats:styled-content>), along with inflammation, were present in TAAD<\/jats:styled-content> samples from both mouse and human. Transcriptional profiling of SMCs<\/jats:styled-content> after mechanical stress demonstrated the expression of genes for ER<\/jats:styled-content> stress and inflammation. To explore the causal role of ER<\/jats:styled-content> stress in initiating degenerative signalling events and TAAD<\/jats:styled-content>, we treated wild\u2010type (CHOP<\/jats:styled-content><\/jats:italic>+\/+<\/jats:sup>) or CHOP<\/jats:styled-content><\/jats:italic>\u2212\/\u2212<\/jats:sup> mice with BAPN<\/jats:styled-content> and found that CHOP<\/jats:styled-content><\/jats:italic> deficiency protected against TAAD<\/jats:styled-content> formation and rupture, as well as reduction in \u03b1\u2010SMA<\/jats:styled-content> level. Both SMC<\/jats:styled-content> apoptosis and inflammation were significantly reduced in CHOP<\/jats:styled-content><\/jats:italic>\u2212\/\u2212<\/jats:sup> mice. Moreover, SMCs<\/jats:styled-content> isolated from CHOP<\/jats:styled-content><\/jats:italic>\u2212\/\u2212<\/jats:sup> mice were resistant to mechanical stress\u2010induced apoptosis.<\/jats:italic> Taken together, our results demonstrated that mechanical stress\u2010induced ER<\/jats:styled-content> stress promotes SMCs<\/jats:styled-content> apoptosis, inflammation and degeneration, providing insight into TAAD<\/jats:styled-content> formation and progression. \u00a9 2015 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.4534","type":"journal-article","created":{"date-parts":[[2015,3,18]],"date-time":"2015-03-18T04:03:50Z","timestamp":1426651430000},"page":"373-383","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":160,"title":["Mechanical stretch\u2010induced endoplasmic reticulum stress, apoptosis and inflammation contribute to thoracic aortic aneurysm and dissection"],"prefix":"10.1002","volume":"236","author":[{"given":"Li\u2010Xin","family":"Jia","sequence":"first","affiliation":[{"name":"Beijing Anzhen Hospital Capital Medical University, Key Laboratory of Remodelling\u2010related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing Institute of Heart, Lung and Blood Vessel Disease Beijing People's Republic of 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