Advances in the pathogenesis of aortic dissection_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

XIE Enzehua , QIU Juntao , WU Jinlin ,  YU Cuntao

Department of Cardiac Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, P.R.China;

Corresponding author：

YU Cuntao, Email: cuntaoyu@126.com

Keywords：

Aortic dissection; pathogenesis; gene; non-coding RNA; review

DOI：

10.7507/1007-4848.202002112

Video：

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Aortic dissection is a catastrophic emergency with a high mortality rate, and its full pathogenesis remains unknown to researchers, which brings a heavy burden to the individuals, society and family because of its poor prognosis. Improving the efficiency of its diagnosis and treatment and defining the pathogenic mechanism clearly is a research hotspot. Recently, utilizing bioinformatics to find diagnostic biomarker of aortic dissection has attracted the attention of many researchers. Besides, exploring the relationship between pathogenic mechanism and inflammatory process, extracellular matrix degradation, elastic fiber fracture and the phenotypic transformation of vascular smooth muscle cells is also a hot topic. We summarize recent progress made in the pathogenesis of aortic dissection. We hope to identify key molecules driving aortic dissection and provide reliable reference for the diagnosis, medical treatment and prevention of aortic dissection.

Citation： XIE Enzehua, QIU Juntao, WU Jinlin, YU Cuntao. Advances in the pathogenesis of aortic dissection. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2020, 27(9): 1081-1086. doi: 10.7507/1007-4848.202002112 Copy

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2.	Maslen CL, Corson GM, Maddox BK, <italic>et al</italic>. Partial sequence of a candidate gene for the Marfan syndrome. Nature, 1991, 352(6333): 334-337.
3.	Renard M, Francis C, Ghosh R, <italic>et al</italic>. Clinical validity of genes for heritable thoracic aortic aneurysm and dissection. J Am Coll Cardiol, 2018, 72(6): 605-615.
4.	Jondeau G, Ropers J, Regalado E, <italic>et al</italic>. International registry of patients carrying TGFBR1 or TGFBR2 mutations: results of the MAC (Montalcino Aortic Consortium). Circ Cardiovasc Genet, 2016, 9(6): 548-558.
5.	Lee VS, Halabi CM, Hoffman EP, <italic>et al</italic>. Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans. Proc Natl Acad Sci USA, 2016, 113(31): 8759-8764.
6.	Guo DC, Regalado ES, Gong L, <italic>et al</italic>. LOX mutations predispose to thoracic aortic aneurysms and dissections. Circ Res, 2016, 118(6): 928-934.
7.	Quiñones-Pérez B, VanNoy GE, Towne MC, <italic>et al</italic>. Three-generation family with novel contiguous gene deletion on chromosome 2p22 associated with thoracic aortic aneurysm syndrome. Am J Med Genet, 2018, 176(3): 560-569.
8.	Guo DC, Regalado ES, Pinard A, <italic>et al</italic>. LTBP3 pathogenic variants predispose individuals to thoracic aortic aneurysms and dissections. Am J Hum Genet, 2018, 102(4): 706-712.
9.	Gould RA, Aziz H, Woods CE, <italic>et al</italic>. ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm. Nat Genet, 2019, 51(1): 42-50.
10.	Tan KL, Haelterman NA, Kwartler CS, <italic>et al</italic>. Ari-1 regulates myonuclear organization together with parkin and is associated with aortic aneurysms. Dev Cell, 2018, 45(2): 226-244.
11.	Kuang SQ, Medina-Martinez O, Guo DC, <italic>et al</italic>. FOXE3 mutations predispose to thoracic aortic aneurysms and dissections. J Clin Investig, 2016, 126(3): 948-961.
12.	Koenig SN, LaHaye S, Feller JD, <italic>et al</italic>. Notch1 haploinsuciency causes ascending aortic aneurysms in mice. JCI Insight, 2017, 2(21): 91353.
13.	Cortini F, Marinelli B, Seia M, <italic>et al</italic>. Next-generation sequencing and a novel COL3A1 mutation associated with vascular Ehlers-Danlos syndrome with severe intestinal involvement: A case report. J Med Case Rep, 2016, 10(1): 303.
14.	Legrand A, Devriese M, Dupuis-Girod S, <italic>et al</italic>. Frequency of de novo variants and parental mosaicism in vascular Ehlers-Danlos syndrome. Genet Med, 2019, 21(7): 1568-1575.
15.	An Z, Liu Y, Song ZG, <italic>et al</italic>. Mechanisms of aortic dissection smooth muscle cell phenotype switch. J Thorac Cardiovasc Surg, 2017, 154(5): 1511-1521.
16.	杨航, 罗明尧, 马艳云, 等. 遗传性胸主动脉瘤/夹层基因检测及临床诊疗专家共识. 中国循环杂志, 2019, 34(4): 319-325.
17.	Meester JA, Vandeweyer G, Pintelon I, <italic>et al</italic>. Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections. Genet Med, 2017, 19(4): 386-395.
18.	Ostberg Nicolai P, Zafar Mohammad A, Ziganshin Bulat A, <italic>et al</italic>. The genetics of thoracic aortic aneurysms and dissection: A clinical perspective. Biomolecules, 2020, 10(2): 182.
19.	Sandeep K, Boon Reinier A, Lars M, <italic>et al</italic>. Role of noncoding RNAs in the pathogenesis of abdominal aortic aneurysm. Circ Res, 2019, 124(4): 619-630.
20.	Dong J, Bao JM, Feng R, <italic>et al</italic>. Circulating microRNAs: a novel potential biomarker for diagnosing acute aortic dissection. Sci Rep, 2017, 7(1): 12784.
21.	Gao P, Si JY, Yang B, <italic>et al</italic>. Upregulation of microRNA-15a contributes to pathogenesis of abdominal aortic aneurysm (AAA) by modulating the expression of cyclin-dependent kinase isnhibitor 2B (CDKN2B). Med Sci Monit, 2017, 23: 881-888.
22.	Naoyuki K, Kyoko F, Mamoru A, <italic>et al</italic>. Gene expression profiling of acute type A aortic dissection combined with in vitro assessment. Eur J Cardiothorac Surg, 2017, 52(4): 810-817.
23.	Huang WH, Huang C, Ding HY, <italic>et al</italic>. Involvement of miR-145 in the development of aortic dissection via inducing proliferation, migration, and apoptosis of vascular smooth muscle cells. J Clin Lab Anal, 2020, 34(1): e23028.
24.	Li TB, Liu CC, Liu LC, <italic>et al</italic>. Regulatory msechanism of microRNA-145 in the pathogenesis of acute aortic dissection. Yonsei Med J, 2019, 60(4): 352-359.
25.	Eftihia S, Panagiota G. MicroRNAs in acute aortic dissection. J Thorac Dis, 2018, 10(3): 1256-1257.
26.	Climent M, Quintavalle M, Miragoli M, <italic>et al</italic>. TGFβ triggers miR-143/145 transfer from smooth muscle cells to endothelial cells, thereby modulating vessel stabilization. Circ Res, 2015, 116(11): 1753.
27.	Li Y, Yang N, Zhou XB, <italic>et al</italic>. LncRNA and mRNA interaction study based on transcriptome profiles reveals potential core genes in the pathogenesis of human thoracic aortic dissection. Mol Med Rep, 2018, 18(3): 3167-3176.
28.	He Q, Tan JY, Yu Bo, <italic>et al</italic>. Long noncoding RNA HIF1A-AS1A reduces apoptosis of vascular smooth muscle cells: implications for the pathogenesis of thoracoabdominal aorta aneurysm. Pharmazie, 2015, 70(5): 310-315.
29.	Sun J, Chen GJ, Jing YW, <italic>et al</italic>. LncRNA expression profile of human thoracic aortic dissection by high-throughput sequencing. Cell Physiol Biochem, 2018, 46(3): 1027-1041.
30.	Zou MH, Huang CX, Li XZ, <italic>et al</italic>. Circular RNA expression profile and potential function of hsa_circRNA_101238 in human thoracic aortic dissection. Oncotarget, 2017, 8(47): 81825-81837.
31.	Tian CC, Tang XL, Zhu XY, <italic>et al</italic>. Expression profiles of circRNAs and the potential diagnostic value of serum circMARK3 in human acute Stanford type A aortic dissection. PLoS One, 2019, 14(6): e0219013.
32.	Tugce S, Arzu A, Tuba G. Potential function of microRNAs in thoracic aortic aneurysm and thoracic aortic dissection pathogenesis. Mol Med Rep, 2019, 20(6): 5353-5362.
33.	Zeng T, Yuan J, Gan JT, <italic>et al</italic>. Thrombospondin 1 is increased in the aorta and plasma of patients with acute aortic dissection. Can J Cardiol, 2019, 35(1): 42-50.
34.	Yang WG, Wen DZ, Chen SX, <italic>et al</italic>. The expression of nsesprin-1 increased in aortic dissection: why? J Thorac Dis, 2019, 11(12): 4960-4965.
35.	Fan FD, Zhou Q, Pan J, <italic>et al</italic>. Preliminary observation of chemokine expression in patients with Stanford type A aortic dissection. Cytokine, 2020, 127: 154920.
36.	Liao MF, Zou SL, Bao Y, <italic>et al</italic>. Matrix metalloproteinases are regulated by MicroRNA 320 in macrophages and are associated with aortic dissection. Exp Cell Res, 2018, 370(1): 98-102.
37.	Milewicz Dianna M, Trybus Kathleen M, Guo DC, <italic>et al</italic>. Altered smooth muscle cell force generation as a driver of thoracic aortic aneurysms and dissections. Arterioscler Thromb Vasc Biol, 2017, 37(1): 26-34.
38.	Brownstei AJ, Kostiuk V, Ziganshin BA, <italic>et al</italic>. Genes associated with thoracic aortic aneurysm and dissection: 2018 update and clinical implications. Aorta, 2018, 6(1): 13-20.
39.	Milewicz D, Hostetler E, Wallace S, <italic>et al</italic>. Precision medical and surgical management for thoracic aortic aneurysms and acute aortic dissections based on the causative mutant gene. J Cardiovasc Surg, 2016, 57(2): 172-177.

1. Evangelista A, Isselbacher EM, Bossone E, <italic>et al</italic>. Insights from the International Registry of Acute Aortic Dissection: A 20-year experience of collaborative clinical research. Circulation, 2018, 137(17): 1846-1860.
2. Maslen CL, Corson GM, Maddox BK, <italic>et al</italic>. Partial sequence of a candidate gene for the Marfan syndrome. Nature, 1991, 352(6333): 334-337.
3. Renard M, Francis C, Ghosh R, <italic>et al</italic>. Clinical validity of genes for heritable thoracic aortic aneurysm and dissection. J Am Coll Cardiol, 2018, 72(6): 605-615.
4. Jondeau G, Ropers J, Regalado E, <italic>et al</italic>. International registry of patients carrying TGFBR1 or TGFBR2 mutations: results of the MAC (Montalcino Aortic Consortium). Circ Cardiovasc Genet, 2016, 9(6): 548-558.
5. Lee VS, Halabi CM, Hoffman EP, <italic>et al</italic>. Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans. Proc Natl Acad Sci USA, 2016, 113(31): 8759-8764.
6. Guo DC, Regalado ES, Gong L, <italic>et al</italic>. LOX mutations predispose to thoracic aortic aneurysms and dissections. Circ Res, 2016, 118(6): 928-934.
7. Quiñones-Pérez B, VanNoy GE, Towne MC, <italic>et al</italic>. Three-generation family with novel contiguous gene deletion on chromosome 2p22 associated with thoracic aortic aneurysm syndrome. Am J Med Genet, 2018, 176(3): 560-569.
8. Guo DC, Regalado ES, Pinard A, <italic>et al</italic>. LTBP3 pathogenic variants predispose individuals to thoracic aortic aneurysms and dissections. Am J Hum Genet, 2018, 102(4): 706-712.
9. Gould RA, Aziz H, Woods CE, <italic>et al</italic>. ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm. Nat Genet, 2019, 51(1): 42-50.
10. Tan KL, Haelterman NA, Kwartler CS, <italic>et al</italic>. Ari-1 regulates myonuclear organization together with parkin and is associated with aortic aneurysms. Dev Cell, 2018, 45(2): 226-244.
11. Kuang SQ, Medina-Martinez O, Guo DC, <italic>et al</italic>. FOXE3 mutations predispose to thoracic aortic aneurysms and dissections. J Clin Investig, 2016, 126(3): 948-961.
12. Koenig SN, LaHaye S, Feller JD, <italic>et al</italic>. Notch1 haploinsuciency causes ascending aortic aneurysms in mice. JCI Insight, 2017, 2(21): 91353.
13. Cortini F, Marinelli B, Seia M, <italic>et al</italic>. Next-generation sequencing and a novel COL3A1 mutation associated with vascular Ehlers-Danlos syndrome with severe intestinal involvement: A case report. J Med Case Rep, 2016, 10(1): 303.
14. Legrand A, Devriese M, Dupuis-Girod S, <italic>et al</italic>. Frequency of de novo variants and parental mosaicism in vascular Ehlers-Danlos syndrome. Genet Med, 2019, 21(7): 1568-1575.
15. An Z, Liu Y, Song ZG, <italic>et al</italic>. Mechanisms of aortic dissection smooth muscle cell phenotype switch. J Thorac Cardiovasc Surg, 2017, 154(5): 1511-1521.
16. 杨航, 罗明尧, 马艳云, 等. 遗传性胸主动脉瘤/夹层基因检测及临床诊疗专家共识. 中国循环杂志, 2019, 34(4): 319-325.
17. Meester JA, Vandeweyer G, Pintelon I, <italic>et al</italic>. Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections. Genet Med, 2017, 19(4): 386-395.
18. Ostberg Nicolai P, Zafar Mohammad A, Ziganshin Bulat A, <italic>et al</italic>. The genetics of thoracic aortic aneurysms and dissection: A clinical perspective. Biomolecules, 2020, 10(2): 182.
19. Sandeep K, Boon Reinier A, Lars M, <italic>et al</italic>. Role of noncoding RNAs in the pathogenesis of abdominal aortic aneurysm. Circ Res, 2019, 124(4): 619-630.
20. Dong J, Bao JM, Feng R, <italic>et al</italic>. Circulating microRNAs: a novel potential biomarker for diagnosing acute aortic dissection. Sci Rep, 2017, 7(1): 12784.
21. Gao P, Si JY, Yang B, <italic>et al</italic>. Upregulation of microRNA-15a contributes to pathogenesis of abdominal aortic aneurysm (AAA) by modulating the expression of cyclin-dependent kinase isnhibitor 2B (CDKN2B). Med Sci Monit, 2017, 23: 881-888.
22. Naoyuki K, Kyoko F, Mamoru A, <italic>et al</italic>. Gene expression profiling of acute type A aortic dissection combined with in vitro assessment. Eur J Cardiothorac Surg, 2017, 52(4): 810-817.
23. Huang WH, Huang C, Ding HY, <italic>et al</italic>. Involvement of miR-145 in the development of aortic dissection via inducing proliferation, migration, and apoptosis of vascular smooth muscle cells. J Clin Lab Anal, 2020, 34(1): e23028.
24. Li TB, Liu CC, Liu LC, <italic>et al</italic>. Regulatory msechanism of microRNA-145 in the pathogenesis of acute aortic dissection. Yonsei Med J, 2019, 60(4): 352-359.
25. Eftihia S, Panagiota G. MicroRNAs in acute aortic dissection. J Thorac Dis, 2018, 10(3): 1256-1257.
26. Climent M, Quintavalle M, Miragoli M, <italic>et al</italic>. TGFβ triggers miR-143/145 transfer from smooth muscle cells to endothelial cells, thereby modulating vessel stabilization. Circ Res, 2015, 116(11): 1753.
27. Li Y, Yang N, Zhou XB, <italic>et al</italic>. LncRNA and mRNA interaction study based on transcriptome profiles reveals potential core genes in the pathogenesis of human thoracic aortic dissection. Mol Med Rep, 2018, 18(3): 3167-3176.
28. He Q, Tan JY, Yu Bo, <italic>et al</italic>. Long noncoding RNA HIF1A-AS1A reduces apoptosis of vascular smooth muscle cells: implications for the pathogenesis of thoracoabdominal aorta aneurysm. Pharmazie, 2015, 70(5): 310-315.
29. Sun J, Chen GJ, Jing YW, <italic>et al</italic>. LncRNA expression profile of human thoracic aortic dissection by high-throughput sequencing. Cell Physiol Biochem, 2018, 46(3): 1027-1041.
30. Zou MH, Huang CX, Li XZ, <italic>et al</italic>. Circular RNA expression profile and potential function of hsa_circRNA_101238 in human thoracic aortic dissection. Oncotarget, 2017, 8(47): 81825-81837.
31. Tian CC, Tang XL, Zhu XY, <italic>et al</italic>. Expression profiles of circRNAs and the potential diagnostic value of serum circMARK3 in human acute Stanford type A aortic dissection. PLoS One, 2019, 14(6): e0219013.
32. Tugce S, Arzu A, Tuba G. Potential function of microRNAs in thoracic aortic aneurysm and thoracic aortic dissection pathogenesis. Mol Med Rep, 2019, 20(6): 5353-5362.
33. Zeng T, Yuan J, Gan JT, <italic>et al</italic>. Thrombospondin 1 is increased in the aorta and plasma of patients with acute aortic dissection. Can J Cardiol, 2019, 35(1): 42-50.
34. Yang WG, Wen DZ, Chen SX, <italic>et al</italic>. The expression of nsesprin-1 increased in aortic dissection: why? J Thorac Dis, 2019, 11(12): 4960-4965.
35. Fan FD, Zhou Q, Pan J, <italic>et al</italic>. Preliminary observation of chemokine expression in patients with Stanford type A aortic dissection. Cytokine, 2020, 127: 154920.
36. Liao MF, Zou SL, Bao Y, <italic>et al</italic>. Matrix metalloproteinases are regulated by MicroRNA 320 in macrophages and are associated with aortic dissection. Exp Cell Res, 2018, 370(1): 98-102.
37. Milewicz Dianna M, Trybus Kathleen M, Guo DC, <italic>et al</italic>. Altered smooth muscle cell force generation as a driver of thoracic aortic aneurysms and dissections. Arterioscler Thromb Vasc Biol, 2017, 37(1): 26-34.
38. Brownstei AJ, Kostiuk V, Ziganshin BA, <italic>et al</italic>. Genes associated with thoracic aortic aneurysm and dissection: 2018 update and clinical implications. Aorta, 2018, 6(1): 13-20.
39. Milewicz D, Hostetler E, Wallace S, <italic>et al</italic>. Precision medical and surgical management for thoracic aortic aneurysms and acute aortic dissections based on the causative mutant gene. J Cardiovasc Surg, 2016, 57(2): 172-177.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Advances in the pathogenesis of aortic dissection

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