Skip to main content

Advertisement

SpringerLink
Log in

Downregulation of LILRB4 Promotes Human Aortic Smooth Muscle Cell Contractile Phenotypic Switch and Apoptosis in Aortic Dissection

  • Research
  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Aortic dissection (AD) is a severe vascular disease with high rates of mortality and morbidity. However, the underlying molecular mechanisms of AD remain unclear. Differentially expressed genes (DEGs) were screened by bioinformatics methods. Alterations of histopathology and inflammatory factor levels in β-aminopropionitrile (BAPN)-induced AD mouse model were evaluated through Hematoxylin–Eosin (HE) staining and Enzyme-linked immunosorbent assay (ELISA), respectively. Reverse transcription quantitative real-time polymerase chain reaction was performed to detect DEGs expression. Furthermore, the role of LILRB4 in AD was investigated through Cell Counting Kit-8 (CCK-8), wound healing, and flow cytometry. Western blotting was employed to assess the phenotypic switch and extracellular matrix (ECM)-associated protein expressions in platelet-derived growth factor-BB (PDGF-BB)-stimulated in vitro model of AD. In the AD mouse model, distinct dissection formation was observed. TNF-α, IL-1β, IL-8, and IL-6 levels were higher in the AD mouse model than in the controls. Six hub genes were identified, including LILRB4, TIMP1, CCR5, CCL7, MSR1, and CLEC4D, all of which were highly expressed. Further exploration revealed that LILRB4 knockdown inhibited the cell vitality and migration of PDGF-BB-induced HASMCs while promoting apoptosis and G0/G1 phase ratio. More importantly, LILRB4 knockdown promoted the protein expression of α-SMA and SM22α, while decreasing the expression of Co1, MMP2, and CTGF, which suggested that LILRB4 silencing promoted contractile phenotypic transition and ECM stability. LILRB4 knockdown inhibits the progression of AD. Our study provides a new potential target for the clinical treatment of AD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data Availability

The datasets analyzed during the current study are available in the National Center for Biotechnology Information (NCBI) repository, [https://www.ncbi.nlm.nih.gov/geo/].

References

  1. Zha, Z., Pan, Y., Zheng, Z., & Wei, X. (2021). Prognosis and risk factors of stroke after thoracic endovascular aortic repair for stanford type B aortic dissection. Frontiers in Cardiovascular Medicine, 8, 787038.

    Article  PubMed  Google Scholar 

  2. Thompson. R., W. (2002). Detection and management of small aortic aneurysms. New England Journal of Medicine, 346(19), 1484-1486

  3. Chen, S. W., Lin, Y. S., Wu, V. C., Lin, M. S., Chou, A. H., Chu, P. H., & Chen, T. H. (2020). Effect of beta-blocker therapy on late outcomes after surgical repair of type A aortic dissection. The Journal of Thoracic and Cardiovascular Surgery, 159(5), 1694–1703.

    Article  PubMed  Google Scholar 

  4. Zhu, S. B., Zhu, J., Zhou, Z. Z., Xi, E. P., Wang, R. P., & Zhang, Y. (2015). TGF-β1 induces human aortic vascular smooth muscle cell phenotype switch through PI3K/AKT/ID2 signaling. American journal of translational research, 7(12), 2764–2774.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Wang, Y., Dong, C. Q., Peng, G. Y., Huang, H. Y., Yu, Y. S., Ji, Z. C., & Shen, Z. Y. (2019). MicroRNA-134–5p regulates media degeneration through Inhibiting VSMC phenotypic switch and migration in thoracic aortic dissection. Molecular. Therapy-Nucleic Acids., 16, 284–924.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Xu, Z., Zhong, K., Guo, G., Xu, C., Song, Z., Wang, D., & Pan, J. (2021). 2021 circ_TGFBR2 Inhibits vascular smooth muscle cells phenotypic switch and suppresses aortic dissection progression by sponging miR-29a. Journal of Inflammation Research., 14, 5877–5890.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cao, G., Xuan, X., Hu, J., Zhang, R., Jin, H., & Dong, H. (2022). How vascular smooth muscle cell phenotype switching contributes to vascular disease. Cell Communication and Signaling: CCS, 20(1), 180.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Davis-Dusenbery, B. N., Wu, C., & Hata, A. (2011). Micromanaging vascular smooth muscle cell differentiation and phenotypic modulation. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(11), 2370–2377.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Huang, W., Huang, C., Ding, H., Luo, J., Liu, Y., Fan, R., Xiao, F., Fan, X., & Jiang, Z. (2020). Involvement of miR-145 in the development of aortic dissection via inducing proliferation, migration, and apoptosis of vascular smooth muscle cells. Journal of clinical laboratory analysis., 34(1), e23028.

    Article  PubMed  Google Scholar 

  10. Meng, J., Liu, H. L., Ma, D., Wang, H. Y., Peng, Y., & Wang, H. L. (2020). Upregulation of aurora kinase A promotes vascular smooth muscle cell proliferation and migration by activating the GSK-3beta/beta-catenin pathway in aortic-dissecting aneurysms. Life Sciences, 262, 118491.

    Article  CAS  PubMed  Google Scholar 

  11. Hu, C., Huang, W., Xiong, N., & Liu, X. (2021). SP1-mediated transcriptional activation of PTTG1 regulates the migration and phenotypic switching of aortic vascular smooth muscle cells in aortic dissection through MAPK signaling. Archives of Biochemistry and Biophysics, 711, 109007.

    Article  CAS  PubMed  Google Scholar 

  12. Yang, K., Ren, J., Li, X., Wang, Z., Xue, L., Cui, S., Sang, W., Xu, T., Zhang, J., Yu, J., & Liu, Z. (2020). Prevention of aortic dissection and aneurysm via an ALDH2-mediated switch in vascular smooth muscle cell phenotype. European Heart Journal., 41(26), 2442–2453.

    Article  CAS  PubMed  Google Scholar 

  13. Yang, T., Qian, Y., Liang, X., Wu, J., Zou, M., & Deng, M. (2022). LILRB4, an immune checkpoint on myeloid cells. Blood Science, 4(2), 49–56.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Liu, J., Wu, Q., Shi, J., Guo, W., Jiang, X., & Zhou, B. (2020). Ren C LILRB4, from the immune system to the disease target. Journal of Translational Research., 12(7), 3149–3166.

    CAS  Google Scholar 

  15. Huang, C., Zhu, H., X., Yao, Y., Bian, Z., H., Zheng, Y., J., Li, L., Moutsopoulos, H,. M,. Gershwin, M,. E,. & Lian, Z,. X, (2019) Immune checkpoint molecules. Possible future therapeutic implications in autoimmune diseases. Journal of Autoimmunity, 104, 102333

  16. Inui, M., Sugahara-Tobinai, A., Fujii, H., Itoh-Nakadai, A., Fukuyama, H., Kurosaki, T., Ishii, T., Harigae, H., & Takai, T. (2016) Tolerogenic immunoreceptor ILT3/LILRB4 paradoxically marks pathogenic auto-antibody-producing plasmablasts and plasma cells in non-treated SLE. International Immunology 28(12), 597–604

  17. Sugahara-Tobinai, A., Inui, M., Metoki, T., Watanabe, Y., Onuma, R., Takai, T., & Kumaki, S. (2019). augmented ILT3/LILRB4 expression of peripheral blood antibody secreting cells in the acute phase of Kawasaki Disease. Pediatric Infectious Disease Journal., 38(4), 431–438.

    Article  PubMed  Google Scholar 

  18. Anami, Y., Deng, M., Gui, X., Yamaguchi, A., Yamazaki, C. M., Zhang, N., Zhang, C. C., An, Z., & Tsuchikama, K. (2020). LILRB4-targeting antibody-drug conjugates for the treatment of acute myeloid Leukemia. Molecular Cancer Therapeutics, 19(11), 2330–2339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lu, Y., Jiang, Z., Dai, H., Miao, R., Shu, J., Gu, H., Liu, X., Huang, Z., Yang, G., Chen, A. F., & Yuan, H. (2018). Hepatic leukocyte immunoglobulin-like receptor B4 (LILRB4) attenuates nonalcoholic fatty liver disease via SHP1-TRAF6 pathway. Hepatology, 67(4), 1303–1309.

    Article  CAS  PubMed  Google Scholar 

  20. Zhou, H., Li, N., Yuan, Y., Jin, Y. G., Wu, Q., Yan, L., Bian, Z. Y., Deng, W., Shen, D. F., Li, H., & Tang, Q. Z. (2020). Leukocyte immunoglobulin-like receptor B4 protects against cardiac hypertrophy via SHP-2-dependent inhibition of the NF-kappaB pathway. Journal of Molecular Medicine (Berl)., 98(5), 691–705.

    Article  CAS  Google Scholar 

  21. Katz, H. R. (2007). Inhibition of pathologic inflammation by leukocyte Ig-like receptor B4 and related inhibitory receptors. Immunological Reviews, 217, 222–230.

    Article  CAS  PubMed  Google Scholar 

  22. Liu, W., Zhang, W., Wang, T., Wu, J., Zhong, X., Gao, K., Liu, Y., He, X., Zhou, Y., Wang, H., & Zeng, H. (2019). Obstructive sleep apnea syndrome promotes the progression of aortic dissection via a ROS- HIF-1alpha-MMPs associated pathway International. Journal of Biological Sciences, 15(13), 2774–2782.

    Google Scholar 

  23. Holycross, B. J., Blank, R. S., Thompson, M. M., Peach, M. J., & Owens, G. K. (1992). Platelet-derived growth factor-BB-induced suppression of smooth muscle cell differentiation. Circulation Research, 71(6), 1525–1532.

    Article  CAS  PubMed  Google Scholar 

  24. Su, M., Yue, Z., Wang, H., Jia, M., Bai, C., Qiu, W., & Chen, J. (2018). Ufmylation Is Activated in Vascular Remodeling and Lipopolysaccharide-Induced Endothelial Cell Injury. DNA and cell biology, 37(5), 426–431.

    Article  CAS  PubMed  Google Scholar 

  25. Cao, T., Zhang, L., Yao, L.,L., Zheng, F., Wang, L., Yang, J.,Y., Guo, L.,Y., Li, X.,Y., Yan, Y.,W., Pan, Y., M., & Jiang, M. (2017) S100B promotes injury-induced vascular remodeling through modulating smooth muscle phenotype. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1863(11), 2772–2782

  26. Meng, W., Liu, S., Li, D., Liu, Z., Yang, H., Sun, B., & Liu, H. (2018). Expression of platelet-derived growth factor B is upregulated in patients with thoracic aortic dissection. Journal of vascular surgery, 68, 3S-13S.

    Article  PubMed  Google Scholar 

  27. Zhang, K., Qi, Y., Wang, M., & Chen, Q. (2022). Long non-coding RNA HIF1A-AS2 modulates the proliferation, migration, and phenotypic switch of aortic smooth muscle cells in aortic dissection via sponging microRNA-33b. Bioengineered, 13(3), 6383–6395.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wang, L., Zhang, J., Fu, W., Guo, D., Jiang, J., & Wang, Y. (2012). Association of smooth muscle cell phenotypes with extracellular matrix disorders in thoracic aortic dissection. Journal of Vascular Surgery, 56(6), 1698–1709.

    Article  PubMed  Google Scholar 

  29. Grond-Ginsbach, C., Pjontek, R., Aksay, S. S., Hyhlik-Durr, A., Bockler, D., & Gross-Weissmann, M. L. (2010). Spontaneous arterial dissection: Phenotype and molecular pathogenesis. Cellular and Molecular Life Sciences, 67(11), 1799–1815.

    Article  CAS  PubMed  Google Scholar 

  30. Rizza, A., Negro, F., Mandigers, T. J., Palmieri, C., Berti, S., & Trimarchi, S. (2023). Endovascular Intervention for Aortic Dissection Is “Ascending” International. Journal of Environmental Research and Public Health, 20(5), 4094.

    Article  PubMed  Google Scholar 

  31. Li, Z., Zhou, C., Tan, L., Chen, P., Cao, Y., Li, X., Yan, J., Zeng, H., Wang, D. W., & Wang, D. W. (2018). A targeted sequencing approach to find novel pathogenic genes associated with sporadic aortic dissection. Science China Life Sciences, 61(12), 1545–1553.

    Article  CAS  PubMed  Google Scholar 

  32. Mitsune, A., Yamada, M., Fujino, N., Numakura, T., Ichikawa, T., Suzuki, A., Matsumoto, S., Mitsuhashi, Y., Itakura, K., Makiguchi, T., & Koarai, A. (2021). Upregulation of leukocyte immunoglobulin-like receptor B4 on interstitial macrophages in COPD; their possible protective role against emphysema formation. Respiratory Research., 22(1), 232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Liu, Y., Zou, L., Tang, H., Li, J., Liu, H., Jiang, X., Jiang, B., Dong, Z., & Fu, W. (2022). Sequencing of Immune Cells in Human Aortic Dissection Tissue Provides Insights Into Immune Cell Heterogeneity. Frontiers in Cardiovascular Medicine., 9, 791875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Akama, T., & Chun, T. H. (2018). Transcription factor 21 (TCF21) promotes proinflammatory interleukin 6 expression and extracellular matrix remodeling in visceral adipose stem cells. Journal of Biological Chemistry, 293(17), 6603–6610.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Tang, J., Kang, Y., Huang, L., Wu, L., & Peng, Y. (2020). TIMP1 preserves the blood-brain barrier through interacting with CD63/integrin beta 1 complex and regulating downstream FAK/RhoA signaling. Acta Pharm Sinica B., 10(6), 987–1003.

    Article  CAS  Google Scholar 

  36. Zhang, X., Wu, D., Choi, J. C., Minard, C. G., Hou, X., Coselli, J. S., Shen, Y. H., & LeMaire, S. A. (2014). Matrix metalloproteinase levels in chronic thoracic aortic dissection. Journal of Surgical Research., 189(2), 348–358.

    Article  CAS  PubMed  Google Scholar 

  37. Corbitt, H., Morris, S. A., Gravholt, C. H., Mortensen, K. H., Tippner-Hedges, R., Silberbach, M., & Maslen GenTAC Registry Investigators, C. L. (2018). TIMP3 and TIMP1 are risk genes for bicuspid aortic valve and aortopathy in Turner syndrome. PLoS Genetics, 14(10), e1007692.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Oppermann, M. (2004). Chemokine receptor CCR5: Insights into structure, function, and regulation. Cellular Signalling, 16(11), 1201–1210.

    Article  CAS  PubMed  Google Scholar 

  39. Xie, C., Ye, F., Zhang, N., Huang, Y., Pan, Y., & Xie, X. (2021). CCL7 contributes to angiotensin II-induced abdominal aortic aneurysm by promoting macrophage infiltration and pro-inflammatory phenotype. Journal of Cellular and Molecular Medicine, 25(15), 7280–7293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kelley, J. L., Ozment, T. R., Li, C., Schweitzer, J. B., & Williams, D. L. (2014). Scavenger receptor-A (CD204): A two-edged sword in health and disease Critical. Reviews in Immunology, 34(3), 241–261.

    CAS  Google Scholar 

  41. Zhang, Z., Jiang, Y., Zhou, Z., Huang, J., Chen, S., Zhou, W., Yang, Q., Bai, H., Zhang, H., Ben, J., & Zhu, X. (2019). Scavenger receptor A1 attenuates aortic dissection via promoting efferocytosis in macrophages. Biochemical Pharmacology., 168, 392–403.

    Article  CAS  PubMed  Google Scholar 

  42. Graham, L. M., Gupta, V., Schafer, G., Reid, D. M., Kimberg, M., Dennehy, K. M, Hornsell, W., G,, Guler, R., Campanero-Rhodes, M., A., Palma, A., S., & Feizi, T. (2012) The C-type lectin receptor CLECSF8 (CLEC4D) is expressed by myeloid cells and triggers cellular activation through Syk kinase. Journal of Biological Chemistry 287(31), 25964 2574

  43. Zhang, H., Chen, T., Zhang, Y., Lin, J., Zhao, W., Shi, Y., Lau, H., Zhang, Y., Yang, M., Xu, C., & Tang, L. (2022). Crucial genes in aortic dissection identified by weighted gene coexpression network analysis. Journal of Immunology Research., 2022, 7585149.

    PubMed  PubMed Central  Google Scholar 

  44. Zhao, Y., Hong, X., Xie, X., Guo, D., Chen, B., Fu, W., & Wang, L. (2022). Preoperative systemic inflammatory response index predicts long-term outcomes in type B aortic dissection after endovascular repair. Frontiers in Immunology., 13, 992463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Gao, H., Sun, X., Liu, Y., Liang, S., Zhang, B., Wang, L., & Ren, J. (2021). Analysis of Hub Genes and the Mechanism of Immune Infiltration in Stanford Type a Aortic Dissection. Frontiers in cardiovascular medicine., 8, 680065.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  46. Del Porto, F., Proietta, M., Tritapepe, L., Miraldi, F., Koverech, A., Cardelli, P., Tabacco, F., De Santis, V., Vecchione, A., Mitterhofer, A. P., & Nofroni, I. (2010). Inflammation and immune response in acute aortic dissection. Annals of Medicine, 42(8), 622–629.

    Article  PubMed  Google Scholar 

  47. Colonna, M., Nakajima, H., & Cella, M. (2000). A family of inhibitory and activating Ig-like receptors that modulate function of lymphoid and myeloid cells. Seminars in Immunology, 12(2), 121–127.

    Article  CAS  PubMed  Google Scholar 

  48. Chao, Y., & Zhang, L. (2022). Biomimetic design of inhibitors of immune checkpoint LILRB4. Biophysical Chemistry, 282, 106746.

    Article  CAS  PubMed  Google Scholar 

  49. Ulges, A., Klein, M., Reuter, S., Gerlitzki, B., Hoffmann, M., Grebe, N., Staudt, V., Stergiou, N., Bohn, T., Brühl, T., J., & Muth, S. (2015) Protein kinase CK2 enables regulatory T cells to suppress excessive TH2 responses in vivo. Nature Immunology 16(3), 267 275

  50. Jiang, Z., Qin, J. J., Zhang, Y., Cheng, W. L., Ji, Y. X., Gong, F. H., Zhu, X. Y., Zhang, Y., She, Z. G., Huang, Z., & Li, H. (2017). LILRB4 deficiency aggravates the development of atherosclerosis and plaque instability by increasing the macrophage inflammatory response via NF-kappaB signaling. Clinical Science, 131(17), 2275–2288.

    Article  CAS  PubMed  Google Scholar 

  51. John, S., Chen, H., Deng, M., Gui, X., Wu, G., Chen, W., Li, Z., Zhang, N., An, Z., & Zhang, C. C. (2018). A Novel Anti-LILRB4 CAR-T Cell for the Treatment of Monocytic AML. Molecular Therapy, 26(10), 2487–2495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Gao, Q., Mo, S., Han, C., Liao, X., Yang, C., Wang, X., et al. (2023). Comprehensive analysis of LILR family genes expression and tumour-infiltrating immune cells in early-stage pancreatic ductal adenocarcinoma. IET Systems Biology, 17(2), 39–57.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Li, J., Gao, A., Zhang, F., Wang, S., Wang, J., Wang, J., Han, S., Yang, Z., Chen, X., Fang, Y., & Jiang, G. (2021). ILT3 promotes tumor cell motility and angiogenesis in non-small cell lung cancer. Cancer Letters, 501, 263–276.

    Article  CAS  PubMed  Google Scholar 

  54. Kim, J. B., Zhao, Q., Nguyen, T., Pjanic, M., Cheng, P., Wirka, R., Travisano, S., Nagao Kundu, M., & R,. (2020). Environment-Sensing Aryl Hydrocarbon Receptor Inhibits the Chondrogenic Fate of Modulated Smooth Muscle Cells in Atherosclerotic Lesions. Circulation, 142(6), 575–590.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Zhang, Y.,N., Xie. B., D., Sun, L., Chen, W., Jiang, S., L., Liu, W., Bian, F., Tian, H., & Li R., K. (2016) Phenotypic switching of vascular smooth muscle cells in the 'normal region' of aorta from atherosclerosis patients is regulated by miR-145. Journal of Cellular and Molecular Medicine 20, (6): 1049 61

  56. Frismantiene, A., Philippova, M., Erne, P., & Resink, T. J. (2018). Smooth muscle cell-driven vascular diseases and molecular mechanisms of VSMC plasticity. Cellular Signalling, 52(48), 64.

    Google Scholar 

  57. Chung, J. C. (2023). Pathology and pathophysiology of the aortic root. Annals of Cardiothoracic Surgery, 12(3), 159–167.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Maguire, E. M., Pearce, S. W. A., Xiao, R., Oo, A. Y., & Xiao, Q. (2019). Matrix metalloproteinase in abdominal aortic aneurysm and aortic dissection. Pharmaceuticals (Basel), 12(3), 118.

    Article  CAS  PubMed  Google Scholar 

  59. Zhou, H., Ren, Y., Xiao, J., He, J., Zhang, Y., Qiu, Z., Huang, Q., Hu, Y., & Chen, L. (2021). Changes in aortic collagen in β-aminopropionitrile-induced acute aortic dissection. Annals of Translational Medicine, 9(20), 1574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sun, L., Wang, C., Yuan, Y., Guo, Z., He, Y., Ma, W., & Zhang, J. (2020) Downregulation of HDAC1 suppresses media degeneration by inhibiting the migration and phenotypic switch of aortic vascular smooth muscle cells in aortic dissection. Journal of Cellular Physiology, 235, (11): 8747 56

  61. Li, J., Yu, C., Yu, K., Chen, Z., Xing, D., Zha, B., Xie, W., & Ouyang, H. (2023). SPINT2 is involved in the proliferation, migration and phenotypic switching of aortic smooth muscle cells: Implications for the pathogenesis of thoracic aortic dissection. Experimental and Therapeutic Medicine, 26(6), 546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhi, K., Yin, R., Guo, H., & Qu, L. (2023). PUM2 regulates the formation of thoracic aortic dissection through EFEMP1. Experimental Cell Research, 427(2), 113602.

    Article  CAS  PubMed  Google Scholar 

  63. Yang, J., Fang, M., Yu, C., Li, Z., Wang, Q., Li, C., Wu, J., & Fan, R. (2023). Human aortic smooth muscle cell regulation by METTL3 via upregulation of m6A NOTCH1 modification and inhibition of NOTCH1. Annals of Translational Medicine., 11(10), 350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lee, J. H., Kim, J., Lee, S. J., Kim, Y. A., Maeng, Y. I., & Park, K. K. (2020). Apoptosis and fibrosis of vascular smooth muscle cells in aortic dissection: An immunohistochemical study International. Journal of Clinical and Experimental Pathology, 13(8), 1962–1969.

    CAS  Google Scholar 

  65. Zhang, W., Wang, M., Gao, K., Zhong, X., Xie, Y., Dai, L., Liu, W., Liu, Y., He, X., & Li, S. (2022). Pharmacologic IRE1α kinase inhibition alleviates aortic dissection by decreasing vascular smooth muscle cells apoptosis International. Journal of Biological Sciences, 18(3), 1053–1064.

    CAS  Google Scholar 

  66. Xiao, Y., Sun, Y., Ma, X., Wang, C., Zhang, L., Wang, J., Wang, G., Li, Z., Tian, W., Zhao, Z., & Jing, Q. (2020). MicroRNA-22 inhibits the apoptosis of vascular smooth muscle cell by targeting p38MAPKα in vascular remodeling of aortic dissection. Molecular Therapy-Nucleic Acids, 22, 1051–1062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Shi, Y., Liu, B., Wang, C. S., & Yang, C. S. (2018). MST1 down-regulation in decreasing apoptosis of aortic dissection smooth muscle cell apoptosis. European Review for Medical and Pharmacological Sciences, 22(7), 2044–2051.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

Science and Technology Plan Project of Health Commission of Jiangxi Province (No. 202410052).

Author information

Authors and Affiliations

  1. Department of Cardiovascular Surgery, The Affiliated Hospital of Shanxi Medical University, Shanxi Cardiovascular Hospital (Institute), Shanxi Clinical Medical Research Center for Cardiovascular Disease, No. 18, Yifen Street, Wanbalin District, Taiyuan City, 030024, Shanxi, China

    Jianxian Xiong, Linyuan Wang, Xin Xiong & Yongzhi Deng

  2. Department of Cardiovascular Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China

    Jianxian Xiong

Authors
  1. Jianxian Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Linyuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yongzhi Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JX: Conceptualization; Formal analysis; Methodology;Writing—original draft; Validation; Resources; LW: Data curation; Investigation; Software; Writing—review & editing; XX: Formal analysis; Resources;Writing—review & editing;Visualization; XYD: Methodology; Project administration; Supervision;Writing—review & editing; Validation; all authors have read and approved the manuscript.

Corresponding author

Correspondence to Yongzhi Deng.

Ethics declarations

Conflict of interest

The author declares that they have no competing interests.

Ethical Approval

All the animal experiments conducted in this study were approval by The Institutional Animal Care and Use Committee of The First Affiliated Hospital of Gannan Medical University (Ethics number: LLSC 2023–153).

Consent for Publication

Not applicable.

Additional information

Handling Editor: Phillip Kopf.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 1872 KB)

Supplementary file2 (DOCX 240 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiong, J., Wang, L., Xiong, X. et al. Downregulation of LILRB4 Promotes Human Aortic Smooth Muscle Cell Contractile Phenotypic Switch and Apoptosis in Aortic Dissection. Cardiovasc Toxicol 24, 225–239 (2024). https://doi.org/10.1007/s12012-023-09824-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-023-09824-3

Keywords

Search

Navigation