High-throughput screening of differential expression of exosomal miRNAs in DeBakey typeⅠacute aortic dissection patients_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHANG Dan , ZHAO Xiang , LIU Xiaoyao , AYITILA Aizezi ,  MA Xiang

The Second Department of Coronary Heart Disease, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, P. R. China;

Corresponding author：

MA Xiang, Email: maxiangxj@yeah.net

Keywords：

Acute aortic dissection; exosomes; miRNAs; bioinformatic analysis

DOI：

10.7507/1007-4848.202111073

Video：

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Objective To evaluate the changes in the expression and significance of serum exosomal miRNAs in patients with DeBakey typeⅠacute aortic dissection (AAD). Methods Twelve male patients with AAD and six healthy male medical examiners from our hospital were retrospectively included in this study. According to the time of chest pain, the AAD patients were divided into an AAD group within 24 h of chest pain onset, aged 47.00±8.79 years and an AAD group within 48 h of chest pain onset, aged 50.17±9.99 years. The healthy males were allocated to a control group, aged 49.17±4.26 years. Serum exosomal miRNAs were isolated, identified and quantified, and then differentially expressed exosomal miRNAs were screened. The bioinformatic analyses such as GO and KEGG were performed on the differentially expressed exosomal miRNAs. Results High-throughput screening results revealed differential expression of AAD serum exosomal miRNAs. The upregulated miRNAs of AAD groups was hsa-miR-574-5p (P<0.05), and downregulated miRNAs were hsa-miR-223-3p, hsa-miR-146b-5p, hsa-miR-15b-5p, and hsa-miR-155-5p (P<0.05). Further bioinformatic analysis of the above miRNAs revealed that they were mainly enriched in signaling pathways such as transforming growth factor-β, cell cycle and endoplasmic reticulum protein synthesis. Conclusion Differential expressions of serum exosomal miRNAs in AAD patients may be related to the pathogenesis of AAD, providing new ideas and clues for further exploration of AAD diagnostic markers and pathogenesis.

Citation： ZHANG Dan, ZHAO Xiang, LIU Xiaoyao, AYITILA Aizezi, MA Xiang. High-throughput screening of differential expression of exosomal miRNAs in DeBakey typeⅠacute aortic dissection patients. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(2): 253-259. doi: 10.7507/1007-4848.202111073 Copy

1.	DeMartino RR, Sen I, Huang Y, et al. Population-based assessment of the incidence of aortic dissection, intramural hematoma, and penetrating ulcer, and its associated mortality from 1995 to 2015. Circ Cardiovasc Qual Outcomes, 2018, 11(8): e004689.
2.	Lio A, Bovio E, Nicolò F, et al. Influence of body mass index on outcomes of patients undergoing surgery for acute aortic dissection: A propensity-matched analysis. Tex Heart Inst J, 2019, 46(1): 7-13.
3.	Volovárová R, Volovár S, Lhotsk J, et al. Aortic dissection and other acute aortic syndromes in the emergency department. Vnitr Lek, 2019, 65(7-8): 506-514.
4.	Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science, 2020, 367(6478): eaau6977.
5.	Whitford W, Guterstam P. Exosome manufacturing status. Future Med Chem, 2019, 11(10): 1225-1236.
6.	Tian J, Popal MS, Zhao Y, et al. Interplay between exosomes and autophagy in cardiovascular diseases: Novel promising target for diagnostic and therapeutic application. Aging Dis, 2019, 10(6): 1302-1310.
7.	Matsuyama H, Suzuki HI. Systems and synthetic microRNA biology: From biogenesis to disease pathogenesis. Int J Mol Sci, 2019, 21(1): 132.
8.	Zhao L, Chen X, Cao Y. New role of microRNA: Carcinogenesis and clinical application in cancer. Acta Biochim Biophys Sin (Shanghai), 2011, 43(11): 831-839.
9.	Liu T, Zhang Q, Zhang J, et al. EVmiRNA: A database of miRNA profiling in extracellular vesicles. Nucleic Acids Res, 2019, 47(D1): D89-D93.
10.	Li K, Cui MZ, Zhang KW, et al. Effect of miR-21 on rat thoracic aortic aneurysm model by regulating the expressions of MMP-2 and MMP-9. Eur Rev Med Pharmacol Sci, 2020, 24(2): 878-884.
11.	Vengrenyuk Y, Nishi H, Long X, et al. Cholesterol loading reprograms the microRNA-143/145-myocardin axis to convert aortic smooth muscle cells to a dysfunctional macrophage-like phenotype. Arterioscler Thromb Vasc Biol, 2015, 35(3): 535-546.
12.	Jiang H, Wang M, Ye J, et al. Serum levels of complement-C1q/tumor necrosis factor-related protein-3 decreased in patients with acute aortic dissection. Am J Cardiol, 2018, 122(7): 1244-1248.
13.	Sun J, Chen G, Jing Y, et al. LncRNA expression profile of human thoracic aortic dissection by high-throughput sequencing. Cell Physiol Biochem, 2018, 46(3): 1027-1041.
14.	Yao J, Shi Z, Ma X, et al. lncRNA GAS5/miR-223/NAMPT axis modulates the cell proliferation and senescence of endothelial progenitor cells through PI3K/AKT signaling. J Cell Biochem, 2019, 120(9): 14518-14530.
15.	Akutsu K. Etiology of aortic dissection. Gen Thorac Cardiovas, 2019, 67(3): 271-276.
16.	Martins JL, Soares F, Paiva L, et al. Primum non nocere': Aortic dissection involving ostium of right coronary artery diagnosed by optical coherence tomography. Coron Artery Dis, 2019, 30(6): 467-468.
17.	Senturk T, Antal A, Gunel T. Potential function of microRNAs in thoracic aortic aneurysm and thoracic aortic dissection pathogenesis. Mol Med Rep, 2019, 20(6): 5353-5362.
18.	Wang Y, Dong CQ, Peng GY, et al. MicroRNA-134-5p regulates media degeneration through inhibiting VSMC phenotypic switch and migration in thoracic aortic dissection. Mol Ther Nucleic Acids, 2019, 16: 284-294.
19.	Černá V, Ostašov P, Pitule P, et al. The expression profile of micrornas in small and large abdominal aortic aneurysms. Cardiol Res Pract, 2019, 2019: 8645840.
20.	Du P, Dong J, Zhang L, et al. Diagnostic implication of circulating microRNAs in acute aortic dissection. J Thorac Dis, 2018, 10(8): E659-E660.
21.	Sun LL, Li WD, Lei FR, et al. The regulatory role of microRNAs in angiogenesis-related diseases. J Cell Mol Med, 2018, 22(10): 4568-4587.
22.	Ji Q, Wang YL, Xia LM, et al. High shear stress suppresses proliferation and migration but promotes apoptosis of endothelial cells co-cultured with vascular smooth muscle cells via down-regulating MAPK pathway. J Cardiothorac Surg, 2019, 14(1): 216.
23.	王玉香, 燕燕, 李永芳, 等. 沉默MAP4K4通过调控PPARγ/ABCA1通路缓解ox-LDL诱导的血管内皮细胞损伤. 中国动脉硬化杂志, 2021, 29(1): 54-59.
24.	Qu D, Ling Z, Tan X, et al. High mobility group protein B1 (HMGB1) interacts with receptor for advanced glycation end products (RAGE) to promote airway smooth muscle cell proliferation through ERK and NF-κB pathways. Int J Clin Exp Pathol, 2019, 12(9): 3268-3278.
25.	Wu J, Niu P, Zhao Y, et al. Impact of miR-223-3p and miR-2909 on inflammatory factors IL-6, IL-1, and TNF-α, and the TLR4/TLR2/NF-κB/STAT3 signaling path-way induced by lipopolysaccharide in human adipose stem cells. PLoS One, 2019, 14(2): 0212063.
26.	Dai GH, Ma PZ, Song XB, et al. MicroRNA-223-3p inhibits the angiogenesis of ischemic cardiac microvascular endothelial cells via affecting RPS6KB1/HIF-1a signal pathway. PLoS One, 2014, 9(10): 108468.
27.	Wang X, Ding YY, Chen Y, et al. MiR-223-3p alleviates vascular endothelial injury by targeting IL6ST in kawasaki disease. Front Pediatr, 2019, 7(3): 288.
28.	Xie B, Zhang C, Kang K, et al. miR-599 inhibits vascular smooth muscle cells proliferation and migration by targeting TGFB2. PLoS One, 2015, 10(11): 0141512.
29.	曹运长, 邓洁, 文红波, 等. miR-155通过调节Caspase-3和FADD表达影响TNF-α诱导的HUVEC凋亡. 中国动脉硬化杂志, 2019, 27(2): 106-113.
30.	Chen L, Zheng SY, Yang CQ, et al. MiR-155-5p inhibits the proliferation and migration of VSMCs and HUVECs in atherosclerosis by targeting AKT1. Eur Rev Med Pharmaco, 2019, 23(5): 2223-2233.
31.	Choi S, Park M, Kim J, et al. TNF-α elicits phenotypic and functional alterations of vascular smooth muscle cells by miR-155-5p-dependent down-regulation of cGMP-dependent kinase 1. J Biol Chem, 2018, 293(38): 14812-14822.

1. DeMartino RR, Sen I, Huang Y, et al. Population-based assessment of the incidence of aortic dissection, intramural hematoma, and penetrating ulcer, and its associated mortality from 1995 to 2015. Circ Cardiovasc Qual Outcomes, 2018, 11(8): e004689.
2. Lio A, Bovio E, Nicolò F, et al. Influence of body mass index on outcomes of patients undergoing surgery for acute aortic dissection: A propensity-matched analysis. Tex Heart Inst J, 2019, 46(1): 7-13.
3. Volovárová R, Volovár S, Lhotsk J, et al. Aortic dissection and other acute aortic syndromes in the emergency department. Vnitr Lek, 2019, 65(7-8): 506-514.
4. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science, 2020, 367(6478): eaau6977.
5. Whitford W, Guterstam P. Exosome manufacturing status. Future Med Chem, 2019, 11(10): 1225-1236.
6. Tian J, Popal MS, Zhao Y, et al. Interplay between exosomes and autophagy in cardiovascular diseases: Novel promising target for diagnostic and therapeutic application. Aging Dis, 2019, 10(6): 1302-1310.
7. Matsuyama H, Suzuki HI. Systems and synthetic microRNA biology: From biogenesis to disease pathogenesis. Int J Mol Sci, 2019, 21(1): 132.
8. Zhao L, Chen X, Cao Y. New role of microRNA: Carcinogenesis and clinical application in cancer. Acta Biochim Biophys Sin (Shanghai), 2011, 43(11): 831-839.
9. Liu T, Zhang Q, Zhang J, et al. EVmiRNA: A database of miRNA profiling in extracellular vesicles. Nucleic Acids Res, 2019, 47(D1): D89-D93.
10. Li K, Cui MZ, Zhang KW, et al. Effect of miR-21 on rat thoracic aortic aneurysm model by regulating the expressions of MMP-2 and MMP-9. Eur Rev Med Pharmacol Sci, 2020, 24(2): 878-884.
11. Vengrenyuk Y, Nishi H, Long X, et al. Cholesterol loading reprograms the microRNA-143/145-myocardin axis to convert aortic smooth muscle cells to a dysfunctional macrophage-like phenotype. Arterioscler Thromb Vasc Biol, 2015, 35(3): 535-546.
12. Jiang H, Wang M, Ye J, et al. Serum levels of complement-C1q/tumor necrosis factor-related protein-3 decreased in patients with acute aortic dissection. Am J Cardiol, 2018, 122(7): 1244-1248.
13. Sun J, Chen G, Jing Y, et al. LncRNA expression profile of human thoracic aortic dissection by high-throughput sequencing. Cell Physiol Biochem, 2018, 46(3): 1027-1041.
14. Yao J, Shi Z, Ma X, et al. lncRNA GAS5/miR-223/NAMPT axis modulates the cell proliferation and senescence of endothelial progenitor cells through PI3K/AKT signaling. J Cell Biochem, 2019, 120(9): 14518-14530.
15. Akutsu K. Etiology of aortic dissection. Gen Thorac Cardiovas, 2019, 67(3): 271-276.
16. Martins JL, Soares F, Paiva L, et al. Primum non nocere': Aortic dissection involving ostium of right coronary artery diagnosed by optical coherence tomography. Coron Artery Dis, 2019, 30(6): 467-468.
17. Senturk T, Antal A, Gunel T. Potential function of microRNAs in thoracic aortic aneurysm and thoracic aortic dissection pathogenesis. Mol Med Rep, 2019, 20(6): 5353-5362.
18. Wang Y, Dong CQ, Peng GY, et al. MicroRNA-134-5p regulates media degeneration through inhibiting VSMC phenotypic switch and migration in thoracic aortic dissection. Mol Ther Nucleic Acids, 2019, 16: 284-294.
19. Černá V, Ostašov P, Pitule P, et al. The expression profile of micrornas in small and large abdominal aortic aneurysms. Cardiol Res Pract, 2019, 2019: 8645840.
20. Du P, Dong J, Zhang L, et al. Diagnostic implication of circulating microRNAs in acute aortic dissection. J Thorac Dis, 2018, 10(8): E659-E660.
21. Sun LL, Li WD, Lei FR, et al. The regulatory role of microRNAs in angiogenesis-related diseases. J Cell Mol Med, 2018, 22(10): 4568-4587.
22. Ji Q, Wang YL, Xia LM, et al. High shear stress suppresses proliferation and migration but promotes apoptosis of endothelial cells co-cultured with vascular smooth muscle cells via down-regulating MAPK pathway. J Cardiothorac Surg, 2019, 14(1): 216.
23. 王玉香, 燕燕, 李永芳, 等. 沉默MAP4K4通过调控PPARγ/ABCA1通路缓解ox-LDL诱导的血管内皮细胞损伤. 中国动脉硬化杂志, 2021, 29(1): 54-59.
24. Qu D, Ling Z, Tan X, et al. High mobility group protein B1 (HMGB1) interacts with receptor for advanced glycation end products (RAGE) to promote airway smooth muscle cell proliferation through ERK and NF-κB pathways. Int J Clin Exp Pathol, 2019, 12(9): 3268-3278.
25. Wu J, Niu P, Zhao Y, et al. Impact of miR-223-3p and miR-2909 on inflammatory factors IL-6, IL-1, and TNF-α, and the TLR4/TLR2/NF-κB/STAT3 signaling path-way induced by lipopolysaccharide in human adipose stem cells. PLoS One, 2019, 14(2): 0212063.
26. Dai GH, Ma PZ, Song XB, et al. MicroRNA-223-3p inhibits the angiogenesis of ischemic cardiac microvascular endothelial cells via affecting RPS6KB1/HIF-1a signal pathway. PLoS One, 2014, 9(10): 108468.
27. Wang X, Ding YY, Chen Y, et al. MiR-223-3p alleviates vascular endothelial injury by targeting IL6ST in kawasaki disease. Front Pediatr, 2019, 7(3): 288.
28. Xie B, Zhang C, Kang K, et al. miR-599 inhibits vascular smooth muscle cells proliferation and migration by targeting TGFB2. PLoS One, 2015, 10(11): 0141512.
29. 曹运长, 邓洁, 文红波, 等. miR-155通过调节Caspase-3和FADD表达影响TNF-α诱导的HUVEC凋亡. 中国动脉硬化杂志, 2019, 27(2): 106-113.
30. Chen L, Zheng SY, Yang CQ, et al. MiR-155-5p inhibits the proliferation and migration of VSMCs and HUVECs in atherosclerosis by targeting AKT1. Eur Rev Med Pharmaco, 2019, 23(5): 2223-2233.
31. Choi S, Park M, Kim J, et al. TNF-α elicits phenotypic and functional alterations of vascular smooth muscle cells by miR-155-5p-dependent down-regulation of cGMP-dependent kinase 1. J Biol Chem, 2018, 293(38): 14812-14822.

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High-throughput screening of differential expression of exosomal miRNAs in DeBakey typeⅠacute aortic dissection patients

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