HSPB6 Deficiency Promotes the Development of Aortic Dissection and Rupture.
Autor: | Gao S; Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Zhang K; Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Zhou C; Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Song J; Department of Cardiovascular Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China., Gu Y; Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Cao F; Department of Surgical Intensive Care Unit, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College/National Center for Cardiovascular Diseases, Beijing, China., Wang J; Department of Surgical Intensive Care Unit, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College/National Center for Cardiovascular Diseases, Beijing, China., Xie E; Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: xieenzehua@fuwaihospital.org., Yu C; Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: cuntaoyu_fuwai@163.com., Qiu J; Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: qiujt0328@163.com. |
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Jazyk: | angličtina |
Zdroj: | Laboratory investigation; a journal of technical methods and pathology [Lab Invest] 2024 Mar; Vol. 104 (3), pp. 100326. Date of Electronic Publication: 2024 Jan 17. |
DOI: | 10.1016/j.labinv.2024.100326 |
Abstrakt: | To better understand the pathogenesis of acute type A aortic dissection, high-sensitivity liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS)-based proteomics and phosphoproteomics approaches were used to identify differential proteins. Heat shock protein family B (small) member 6 (HSPB6) in aortic dissection was significantly reduced in human and mouse aortic dissection samples by real-time PCR, western blotting, and immunohistochemical staining techniques. Using an HSPB6-knockout mouse, we investigated the potential role of HSPB6 in β-aminopropionitrile monofumarate-induced aortic dissection. We found increased mortality and increased probability of ascending aortic dissection after HSPB6 knockout compared with wild-type mice. Mechanistically, our data suggest that HSPB6 deletion promoted vascular smooth muscle cell apoptosis. More importantly, HSPB6 deletion attenuated cofilin activity, leading to excessive smooth muscle cell stiffness and eventually resulting in the development of aortic dissection and rupture. Our data suggest that excessive stiffness of vascular smooth muscle cells caused by HSPB6 deficiency is a new pathogenetic mechanism leading to aortic dissection. (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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