TLR4/NF-κB signaling pathway regulates inflammatory response involved in pathophysiological mechanisms of type A aortic dissection_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LIN Zhenye , WANG Zhiwen , MENG Weixin , CHI Chao , ZHAN Xu ,  LIU Hongyu

Department of Cardiac Vascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, P.R.China;

Corresponding author：

LIU Hongyu, Email: hyliu1963@163.com

Keywords：

Stanford type A aortic dissection; immunity-inflammation; toll-like receptors-4; biomarker

DOI：

10.7507/1007-4848.201811021

Video：

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Objective To investigate activated toll-like receptor-4 (TLR4) signaling pathway involved in pathophysiological mechanisms of type A aortic dissection (TAAD). Methods Specimens of full-thickness ascending aorta wall from the TAAD patients (n=12) and the controlled donors (n=12) were collected. Western blotting was used to examine the associated proteins' expression of TLR4 signaling pathway. Blood samples from TAAD (n=43) and controlled patients (n=50) were examined by enzyme-linked immunosorbent assay (ELISA) to detect the circulating plasma cytokines levels of interleukin-1β (L-1β). Results In the aortic wall of TAAD, expression levels of TLR4 and protein expression of major molecule significantly elevated, and activated macrophages increased. Furthermore, elevated IL-1β levels were observed in the TAAD patients’ plasma compared with the control plasma. Multiple logistic regression analysis and receiver operating characteristic (ROC) curve showed that elevated IL-1β could be a novel and promising biomarker with important diagnostic and predictive value in the identification of TAAD. Conclusion Activated TLR4/NF-κB signaling pathway regulates inflammatory response to involve in pathophysiological mechanisms of type A aortic dissection and its regulated inflammatory products have important predictive value for patients with TAAD.

Citation： LIN Zhenye, WANG Zhiwen, MENG Weixin, CHI Chao, ZHAN Xu, LIU Hongyu. TLR4/NF-κB signaling pathway regulates inflammatory response involved in pathophysiological mechanisms of type A aortic dissection. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2019, 26(8): 748-753. doi: 10.7507/1007-4848.201811021 Copy

1.	Parve S, Ziganshin BA, Elefteriades JA. Overview of the current knowledge on etiology, natural history and treatment of aortic dissection. J Cardiovasc Surg, 2017, 58(2): 238.
2.	Pape LA, Awais M, Woznicki EM, et al. Presentation, diagnosis, and outcomes of acute aortic dissection: 17-year trends from the International Registry of Acute Aortic Dissection. J Am Coll Cardiol, 2015, 66(4): 350-358.
3.	Nienaber CA, Clough RE. Management of acute aortic dissection. Lancet, 2015, 385(9970): 800-811.
4.	Luo F, Zhou XL, Li JJ, et al. Inflammatory response is associated with aortic dissection. Ageing Res Rev, 2009, 8(1): 31-35.
5.	He R, Guo DC, Estrera AL, et al. Characterization of the inflammatory and apoptotic cells in the aortas of patients with ascending thoracic aortic aneurysms and dissections. J Thorac Cardiovasc Surg, 2006, 131(3): 671-678.
6.	Cifani N, Proietta M, Tritapepe L, et al. Stanford-A acute aortic dissection, inflammation, and metalloproteinases: A review. Ann Med, 2015, 47(6): 1-6.
7.	Porto FD, Proietta M, Tritapepe L, et al. Inflammation and immune response in acute aortic dissection. Ann Med, 2010, 42(8): 622-629.
8.	Erbel R, Aboyans V, Boileau C, et al. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases. Kardiol Pol, 2014, 72(12): 1169-1252.
9.	Pisano C, Balistreri CR, Ricasoli A, et al. Cardiovascular disease in ageing: an overview on thoracic aortic aneurysm as an emerging inflammatory disease. Mediators Inflamm, 2017, 2017: 1274034.
10.	Schaefer L, Babelova A, Kiss E, et al. The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. J Clin Invest, 2005, 115(8): 2223-2233.
11.	Bjorkbacka H, Fitzgerald KA, Huet F, et al. The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades. Physiol Genomics, 2004, 19(3): 319-330.
12.	Yamamoto M, Sato S, Hemmi H, et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science, 2003, 301(5633): 640-643.
13.	Zeng-Brouwers J, Beckmann J, Nastase MV, et al. De novo expression of circulating biglycan evokes an innate inflammatory tissue response via MyD88/TRIF pathways. Matrix Biol, 2014, 35: 132-142.
14.	Balistreri CR, Candore G, Accardi G, et al. NF-kappaB pathway activators as potential ageing biomarkers: targets for new therapeutic strategies. Immun Ageing, 2013, 10(1): 24.
15.	Raffort J, Lareyre F, Clement M, et al. Monocytes and macrophages in abdominal aortic aneurysm. Nat Rev Cardiol, 2017, 14(8): 457-471.
16.	Yu M, Wang H, Ding A, et al. HMGB1 signals through toll-like receptor (TLR) 4 and TLR2. Shock, 2006, 26(2): 174-179.
17.	Johnston WF, Salmon M, Pope NH, et al. Inhibition of interleukin-1β decreases aneurysm formation and progression in a novel model of thoracic aortic aneurysms. Circulation, 2014, 130(11 Suppl 1): S51-S59.
18.	Reginelli A, Capasso R, Ciccone V, et al. Usefulness of triphasic CT aortic angiography in acute and surveillance: Our experience in the assessment of acute aortic dissection and endoleak. Int J Surg, 2016, 33(Suppl 1): S76-S84.
19.	Lichtenberger JP, Franco DF, Kim JS, et al. MR imaging of thoracic aortic disease. Top Magn Reson Imaging, 2018, 27(2): 95-102.

1. Parve S, Ziganshin BA, Elefteriades JA. Overview of the current knowledge on etiology, natural history and treatment of aortic dissection. J Cardiovasc Surg, 2017, 58(2): 238.
2. Pape LA, Awais M, Woznicki EM, et al. Presentation, diagnosis, and outcomes of acute aortic dissection: 17-year trends from the International Registry of Acute Aortic Dissection. J Am Coll Cardiol, 2015, 66(4): 350-358.
3. Nienaber CA, Clough RE. Management of acute aortic dissection. Lancet, 2015, 385(9970): 800-811.
4. Luo F, Zhou XL, Li JJ, et al. Inflammatory response is associated with aortic dissection. Ageing Res Rev, 2009, 8(1): 31-35.
5. He R, Guo DC, Estrera AL, et al. Characterization of the inflammatory and apoptotic cells in the aortas of patients with ascending thoracic aortic aneurysms and dissections. J Thorac Cardiovasc Surg, 2006, 131(3): 671-678.
6. Cifani N, Proietta M, Tritapepe L, et al. Stanford-A acute aortic dissection, inflammation, and metalloproteinases: A review. Ann Med, 2015, 47(6): 1-6.
7. Porto FD, Proietta M, Tritapepe L, et al. Inflammation and immune response in acute aortic dissection. Ann Med, 2010, 42(8): 622-629.
8. Erbel R, Aboyans V, Boileau C, et al. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases. Kardiol Pol, 2014, 72(12): 1169-1252.
9. Pisano C, Balistreri CR, Ricasoli A, et al. Cardiovascular disease in ageing: an overview on thoracic aortic aneurysm as an emerging inflammatory disease. Mediators Inflamm, 2017, 2017: 1274034.
10. Schaefer L, Babelova A, Kiss E, et al. The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. J Clin Invest, 2005, 115(8): 2223-2233.
11. Bjorkbacka H, Fitzgerald KA, Huet F, et al. The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades. Physiol Genomics, 2004, 19(3): 319-330.
12. Yamamoto M, Sato S, Hemmi H, et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science, 2003, 301(5633): 640-643.
13. Zeng-Brouwers J, Beckmann J, Nastase MV, et al. De novo expression of circulating biglycan evokes an innate inflammatory tissue response via MyD88/TRIF pathways. Matrix Biol, 2014, 35: 132-142.
14. Balistreri CR, Candore G, Accardi G, et al. NF-kappaB pathway activators as potential ageing biomarkers: targets for new therapeutic strategies. Immun Ageing, 2013, 10(1): 24.
15. Raffort J, Lareyre F, Clement M, et al. Monocytes and macrophages in abdominal aortic aneurysm. Nat Rev Cardiol, 2017, 14(8): 457-471.
16. Yu M, Wang H, Ding A, et al. HMGB1 signals through toll-like receptor (TLR) 4 and TLR2. Shock, 2006, 26(2): 174-179.
17. Johnston WF, Salmon M, Pope NH, et al. Inhibition of interleukin-1β decreases aneurysm formation and progression in a novel model of thoracic aortic aneurysms. Circulation, 2014, 130(11 Suppl 1): S51-S59.
18. Reginelli A, Capasso R, Ciccone V, et al. Usefulness of triphasic CT aortic angiography in acute and surveillance: Our experience in the assessment of acute aortic dissection and endoleak. Int J Surg, 2016, 33(Suppl 1): S76-S84.
19. Lichtenberger JP, Franco DF, Kim JS, et al. MR imaging of thoracic aortic disease. Top Magn Reson Imaging, 2018, 27(2): 95-102.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

TLR4/NF-κB signaling pathway regulates inflammatory response involved in pathophysiological mechanisms of type A aortic dissection

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