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Abstract

β-Aminopropionitrile fumarate administration induced thoracic aortic aneurysm and dissection formation in C57/BL6 mice. The incidence of thoracic aortic aneurysm and dissection was >80% (16/18), and half of the mice died of rupture (10/18).1Jia L.X. Zhang W.M. Zhang H.J. Li T.T. Wang Y.L. Qin Y.W. et al.Mechanical stretch-induced endoplasmic reticulum stress, apoptosis and inflammation contribute to thoracic aortic aneurysm and dissection.J Pathol. 2015; 236: 373-383Crossref PubMed Scopus (127) Google Scholar The incidence could be 100% with the administration of β-aminopropionitrile fumarate and angiotensin II.2Kurihara T. Shimizu-Hirota R. Shimoda M. Adachi T. Shimizu H. Weiss S.J. et al.Neutrophil-derived matrix metalloproteinase 9 triggers acute aortic dissection.Circulation. 2012; 126: 3070-3080Crossref PubMed Scopus (170) Google Scholar It was first reported that mechanistic target of rapamycin (mTOR) complexes 1 and 2 are increased in human thoracic aortic aneurysm samples from patients with tricuspid and bicuspid aortic valves.3Jbeli A.H. Hagler M.A. Kunkala M. Roos C.M. Sundt T.M. Miller J.D. Evidence for increased mTORC1 and mTORC2 signaling in human thoracic aortic aneurysm.Circulation. 2018; 128: A18040Google Scholar Cao et al4Cao J. Wu Q. Geng L. Chen X. Shen W. Wu F. et al.Rapamycin inhibits CaCl2-induced thoracic aortic aneurysm formation in rats through mTOR-mediated suppression of proinflammatory mediators.Mol Med Rep. 2017; 16: 1911-1919Crossref Scopus (10) Google Scholar found that significantly enhanced phosphorylation of mTOR was observed in the CaCl2-treated aortic segments. The CaCl2-induced thoracic aortic aneurysm formation was inhibited by preadministration of rapamycin to CaCl2-treated rats. Further in vitro cell culture experiments using aortic smooth muscle cells (SMCs) suggested that the inhibition of the mTOR signaling pathway by rapamycin could promote the differentiation of SMCs.4Cao J. Wu Q. Geng L. Chen X. Shen W. Wu F. et al.Rapamycin inhibits CaCl2-induced thoracic aortic aneurysm formation in rats through mTOR-mediated suppression of proinflammatory mediators.Mol Med Rep. 2017; 16: 1911-1919Crossref Scopus (10) Google Scholar It was investigated that mTOR signaling is overactivated in aortic SMCs, which contributes to murine abdominal aortic aneurysm. Inhibition of the mTOR pathway preserved the contractile phenotype of SMCs.5Li G. Qin L. Wang L. Li X. Caulk A.W. Zhang J. et al.Inhibition of the mTOR pathway in abdominal aortic aneurysm: implications of smooth muscle cell contractile phenotype, inflammation, and aneurysm expansion.Am J Physiol Heart Circ Physiol. 2017; 312: H1110-H1119Crossref PubMed Scopus (29) Google Scholar Thank you so much for your questions. Regarding “Rapamycin prevents thoracic aortic aneurysm and dissection in mice”Journal of Vascular SurgeryVol. 70Issue 1PreviewZhou et al1 recently reported that mechanistic target of rapamycin (mTOR) signaling is activated in β-aminopropionitrile fumarate (BAPN)-treated mice with thoracic aortic aneurysm and dissection (TAAD). Notably, they found that rapamycin could prevent TAAD formation in vivo. Inhibition of mTOR signaling, reduction of inflammatory cell infiltration, and matrix metalloproteinase 9 (MMP-9) production in tissue were used to explain the protective mechanisms of rapamycin. Consequently, they recommended strategies to inhibit the target of rapamycin pathway to treat TAAD. Full-Text PDF Open Archive