Identification and functional analysis of pyroptosis-related miRNAs in aortic dissection_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

GULINAZI·Yesitayi ¹ , WANG Qi ¹ , YILIHAMUJIANG·Keyoumu ² ,  MA Xiang ¹

1. Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, P. R. China;
2. Department of Cardiovascular Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, P. R. China;

Corresponding author：

MA Xiang, Email: maxiangxj@yeah.net

Keywords：

Acute aortic dissection; pyroptosis; miRNAs

DOI：

10.7507/1007-4848.202305023

Video：

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Objective To screen pyroptosis-related miRNAs of acute aortic dissection (AAD) from the GEO database, and analyze and verify their functions. Methods The microarray data set based on the miRNA chip in the GEO database was downloaded, the differentially expressed miRNAs were screened, and the target genes were predicted by the miRWalk database. Pyroptosis-related genes (PRGs) were searched in the PubMed database with "pyroptosis" as the keyword, and the intersection of PRGs and differential miRNAs predicting target genes were taken as AAD PRGs by Venn diagram. GO and KEGG enrichment analyses were performed. CytoHubba was used to screen the critical AAD PRGs and then the AAD pyroptosis-related miRNAs were identified. Aortic tissues were collected from gender- and age-matched AAD patients and healthy people, and the critical PRGs and miRNAs were verified by Western blotting and RT-qPCR. Results A total of 46 AAD differentially expressed miRNAs were screened, and 49 AAD PRGs were obtained by Venn diagram. GO enrichment analysis showed that the genes played a vital role in apoptosis regulated by cysteine endopeptidases. KEGG analysis showed that the genes enriched in Salmonella infection, necroptosis, and Nod-like receptor signaling pathways. CytoHubba screened the critical AAD PRGs such as cysteine aspartase-1 (Caspase-1), tumor necrosis factor (IL)-1β, and tumor necrosis factor (TNF), then obtained 12 AAD pyroptosis-related miRNAs. Aortic tissues were collected from 6 AAD patients and 6 healthy people. There were 5 males and 1 females in the AAD group with an average age of 48.70±6.35 years, and 4 males and 2 females in the healty control group with an average age of 45.30±4.58 years. There was no statistical difference between the two groups in terms of gender, age, smoking history, hypertension, diabetes, or coronary heart disease (P>0.05). Western blotting and RT-qPCR results showed that Caspase-1 was up-regulated in the AAD patients' aortic tissues compared with the healthy aorta, and the corresponding miRNAs were miR-198, miR-3202, and miR-514b-5p, which were all down-regulated. Conclusion Through bioinformatics analysis and verification, the critical AAD PRGs are Caspase-1, IL-1β, and TNF, and Caspase-1 is up-regulated and 3 corresponding pyroptosis-related miRNAs are down-regulated, which provides new ideas for the molecular mechanism and targeted therapy of AAD cell pyroptosis.

Citation： GULINAZI·Yesitayi, WANG Qi, YILIHAMUJIANG·Keyoumu, MA Xiang. Identification and functional analysis of pyroptosis-related miRNAs in aortic dissection. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2024, 31(8): 1181-1189. doi: 10.7507/1007-4848.202305023 Copy

1.	Saremi F, Hassani C, Lin LM, et al. Image predictors of treatment outcome after thoracic aortic dissection repair. Radiographics, 2018, 38(7): 1949-1972.
2.	Roth GA, Mensah GA, Johnson CO, et al. Global burden of cardiovascular diseases and risk factors, 1990-2019: Update from the GBD 2019 study. J Am Coll Cardiol, 2020, 76(25): 2982-3021.
3.	Kapil A, Basha A, Yadav S. Double aortic valve sign in aortic dissection. J Emerg Med, 2022, 62(3): 397-398.
4.	Salmasi MY, Al-Saadi N, Hartley P, et al. The risk of misdiagnosis in acute thoracic aortic dissection: A review of current guidelines. Heart, 2020, 106(12): 885-891.
5.	Hemli JM, Pupovac SS, Gleason TG, et al. Management of acute type A aortic dissection in the elderly: An analysis from IRAD. Eur J Cardiothorac Surg, 2022, 61(4): 838-846.
6.	Chakraborty A, Li Y, Zhang C, et al. Programmed cell death in aortic aneurysm and dissection: A potential therapeutic target. J Mol Cell Cardiol, 2022, 163: 67-80.
7.	Toldo S, Mezzaroma E, Buckley LF, et al. Targeting the NLRP3 inflammasome in cardiovascular diseases. Pharmacol Ther, 2022, 236: 108053.
8.	Sharma M, de Alba E. Structure, activation and regulation of NLRP3 and AIM2 inflammasomes. Int J Mol Sci, 2021, 22(2): 872.
9.	Bai B, Yang Y, Wang Q, et al. NLRP3 inflammasome in endothelial dysfunction. Cell Death Dis, 2020, 11(9): 776.
10.	Ren P, Wu D, Appel R, et al. Targeting the NLRP3 inflammasome with inhibitor MCC950 prevents aortic aneurysms and dissections in mice. J Am Heart Assoc, 2020, 9(7): e014044.
11.	Zuo YB, Zhang YF, Zhang R, et al. Ferroptosis in cancer progression: Role of noncoding RNAs. Int J Biol Sci, 2022, 18(5): 1829-1843.
12.	Ding W, Liu Y, Su Z, et al. Emerging role of non-coding RNAs in aortic dissection. Biomolecules, 2022, 12(10): 1336.
13.	Morelli VM, Brækkan SK, Hansen JB. Role of microRNAs in venous thromboembolism. Int J Mol Sci, 2020, 21(7): 2602.
14.	Huang X, Yue Z, Wu J, et al. MicroRNA-21 knockout exacerbates angiotensinⅡ-induced thoracic aortic aneurysm and dissection in mice with abnormal transforming growth factor-β-SMAD3 signaling. Arterioscler Thromb Vasc Biol, 2018, 38(5): 1086-1101.
15.	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.
16.	Isselbacher EM, Preventza O, et al. 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol, 2022, 80(24): e223-e393.
17.	Alvandi Z, Bischoff J. Endothelial-mesenchymal transition in cardiovascular disease. Arterioscler Thromb Vasc Biol, 2021, 41(9): 2357-2369.
18.	Taggart M. Vascular function in health and disease review series. J Cell Mol Med, 2010, 14(5): 1017.
19.	Fang Y, Tian S, Pan Y, et al. Pyroptosis: A new frontier in cancer. Biomed Pharmacother, 2020, 121: 109595.
20.	Li S, Sun Y, Song M, et al. NLRP3/caspase-1/GSDMD-mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression. JCI Insight, 2021, 6(23): e146852.
21.	Cheng Q, Pan J, Zhou ZL, et al. Caspase-11/4 and gasdermin D-mediated pyroptosis contributes to podocyte injury in mouse diabetic nephropathy. Acta Pharmacol Sin, 2021, 42(6): 954-963.
22.	Sarhan J, Liu BC, Muendlein HI, et al. Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during Yersinia infection. Proc Natl Acad Sci U S A, 2018, 115(46): E10888-E10897.
23.	Jiang M, Qi L, Li L, et al. The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer. Cell Death Discov, 2020, 6: 112.
24.	Sundaram GM, Common JE, Gopal FE, et al. 'See-saw' expression of microRNA-198 and FSTL1 from a single transcript in wound healing. Nature, 2013, 495(7439): 103-106.
25.	Shi L, Kan J, Zhuo L, et al. Bioinformatics identification of miR-514b-5p promotes NSCLC progression and induces PI3K/AKT and p38 pathways by targeting small glutamine-rich tetratricopeptide repeat-containing protein beta. FEBS J, 2023, 290(4): 1134-1150.
26.	Soliman HAN, Toso EA, Darwish IE, et al. Antiapoptotic Protein FAIM2 is targeted by miR-3202, and DUX4 via TRIM21, leading to cell death and defective myogenesis. Cell Death Dis, 2022, 13(4): 405.
27.	Gao Q, Ye Z, Liu T, et al. Hsa-miR-3202 attenuates Jurkat cell infiltration via MMP2 in primary Sjögren's syndrome. J Oral Pathol Med, 2022, 51(9): 818-828.
28.	Shen W, Liu J, Fan M, et al. MiR-3202 protects smokers from chronic obstructive pulmonary disease through inhibiting FAIM2: An in vivo and in vitro study. Exp Cell Res, 2018, 362(2): 370-377.

1. Saremi F, Hassani C, Lin LM, et al. Image predictors of treatment outcome after thoracic aortic dissection repair. Radiographics, 2018, 38(7): 1949-1972.
2. Roth GA, Mensah GA, Johnson CO, et al. Global burden of cardiovascular diseases and risk factors, 1990-2019: Update from the GBD 2019 study. J Am Coll Cardiol, 2020, 76(25): 2982-3021.
3. Kapil A, Basha A, Yadav S. Double aortic valve sign in aortic dissection. J Emerg Med, 2022, 62(3): 397-398.
4. Salmasi MY, Al-Saadi N, Hartley P, et al. The risk of misdiagnosis in acute thoracic aortic dissection: A review of current guidelines. Heart, 2020, 106(12): 885-891.
5. Hemli JM, Pupovac SS, Gleason TG, et al. Management of acute type A aortic dissection in the elderly: An analysis from IRAD. Eur J Cardiothorac Surg, 2022, 61(4): 838-846.
6. Chakraborty A, Li Y, Zhang C, et al. Programmed cell death in aortic aneurysm and dissection: A potential therapeutic target. J Mol Cell Cardiol, 2022, 163: 67-80.
7. Toldo S, Mezzaroma E, Buckley LF, et al. Targeting the NLRP3 inflammasome in cardiovascular diseases. Pharmacol Ther, 2022, 236: 108053.
8. Sharma M, de Alba E. Structure, activation and regulation of NLRP3 and AIM2 inflammasomes. Int J Mol Sci, 2021, 22(2): 872.
9. Bai B, Yang Y, Wang Q, et al. NLRP3 inflammasome in endothelial dysfunction. Cell Death Dis, 2020, 11(9): 776.
10. Ren P, Wu D, Appel R, et al. Targeting the NLRP3 inflammasome with inhibitor MCC950 prevents aortic aneurysms and dissections in mice. J Am Heart Assoc, 2020, 9(7): e014044.
11. Zuo YB, Zhang YF, Zhang R, et al. Ferroptosis in cancer progression: Role of noncoding RNAs. Int J Biol Sci, 2022, 18(5): 1829-1843.
12. Ding W, Liu Y, Su Z, et al. Emerging role of non-coding RNAs in aortic dissection. Biomolecules, 2022, 12(10): 1336.
13. Morelli VM, Brækkan SK, Hansen JB. Role of microRNAs in venous thromboembolism. Int J Mol Sci, 2020, 21(7): 2602.
14. Huang X, Yue Z, Wu J, et al. MicroRNA-21 knockout exacerbates angiotensinⅡ-induced thoracic aortic aneurysm and dissection in mice with abnormal transforming growth factor-β-SMAD3 signaling. Arterioscler Thromb Vasc Biol, 2018, 38(5): 1086-1101.
15. 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.
16. Isselbacher EM, Preventza O, et al. 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol, 2022, 80(24): e223-e393.
17. Alvandi Z, Bischoff J. Endothelial-mesenchymal transition in cardiovascular disease. Arterioscler Thromb Vasc Biol, 2021, 41(9): 2357-2369.
18. Taggart M. Vascular function in health and disease review series. J Cell Mol Med, 2010, 14(5): 1017.
19. Fang Y, Tian S, Pan Y, et al. Pyroptosis: A new frontier in cancer. Biomed Pharmacother, 2020, 121: 109595.
20. Li S, Sun Y, Song M, et al. NLRP3/caspase-1/GSDMD-mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression. JCI Insight, 2021, 6(23): e146852.
21. Cheng Q, Pan J, Zhou ZL, et al. Caspase-11/4 and gasdermin D-mediated pyroptosis contributes to podocyte injury in mouse diabetic nephropathy. Acta Pharmacol Sin, 2021, 42(6): 954-963.
22. Sarhan J, Liu BC, Muendlein HI, et al. Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during Yersinia infection. Proc Natl Acad Sci U S A, 2018, 115(46): E10888-E10897.
23. Jiang M, Qi L, Li L, et al. The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer. Cell Death Discov, 2020, 6: 112.
24. Sundaram GM, Common JE, Gopal FE, et al. 'See-saw' expression of microRNA-198 and FSTL1 from a single transcript in wound healing. Nature, 2013, 495(7439): 103-106.
25. Shi L, Kan J, Zhuo L, et al. Bioinformatics identification of miR-514b-5p promotes NSCLC progression and induces PI3K/AKT and p38 pathways by targeting small glutamine-rich tetratricopeptide repeat-containing protein beta. FEBS J, 2023, 290(4): 1134-1150.
26. Soliman HAN, Toso EA, Darwish IE, et al. Antiapoptotic Protein FAIM2 is targeted by miR-3202, and DUX4 via TRIM21, leading to cell death and defective myogenesis. Cell Death Dis, 2022, 13(4): 405.
27. Gao Q, Ye Z, Liu T, et al. Hsa-miR-3202 attenuates Jurkat cell infiltration via MMP2 in primary Sjögren's syndrome. J Oral Pathol Med, 2022, 51(9): 818-828.
28. Shen W, Liu J, Fan M, et al. MiR-3202 protects smokers from chronic obstructive pulmonary disease through inhibiting FAIM2: An in vivo and in vitro study. Exp Cell Res, 2018, 362(2): 370-377.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Identification and functional analysis of pyroptosis-related miRNAs in aortic dissection

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