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Depleted miR-125a-5p Causes Vascular Endothelial Cell Dysfunction in Deep Vein Thrombosis by Targeting Angiopoietin 2

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Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

Abstract

Deep vein thrombosis (DVT) is a common and fatal disease with a pathology involving endothelial dysfunction. The present research aimed to address the potential clinical significance of miR-125a-5p in DVT and its effect on the dysfunction of Human umbilical vein endothelial cells (HUVECs). Serum miR-125a-5p levels were measured using RT-qPCR in 88 patients with DVT and 76 healthy controls. ROC was plotted to evaluate the diagnostic potential of miR-125a-5p. Spearman’s correlation coefficient was performed to calculate the correlation between miR-125a-5p and clinical indicators. CCK-8, Transwell, and ELISA were employed to verify the effects of cell proliferation, migration, and inflammatory and adhesion molecules. Dual-luciferase reporter assay to analyze potential target for miR-125a-5p. Serum miR-125a-5p was reduced in patients with DVT compared with healthy controls (P < 0.001). ROC showed that miR-125a-5p significantly identified patients with DVT from the healthy controls (AUC = 0.834). Furthermore, serum miR-125a-5p was negatively correlated with inflammatory factors and coagulation factors. In in vitro studies, proliferation and migration of HUVECs were inhibited by suppressed miR-125a-5p, whereas inflammation and adhesion factors were considerably promoted (P < 0.05). Moreover, miR-125-5p directly targeted the 3’UTR of angiopoietin 2 (ANGPT2) and was negatively regulated. Finally, serum ANGPT2 was elevated in patients with DVT and was negatively correlated with serum miR-125a-5p. The current research demonstrated that decreased miR-125a-5p was a novel potential diagnostic biomarker for DVT and that it may be involved in DVT progression by targeting ANGPT2 to regulate endothelial dysfunction.

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References

  1. Sun LL, Xiao L, Du XL, Hong L, Li CL, Jiao J et al (2019) MiR-205 promotes endothelial progenitor cell angiogenesis and deep vein thrombosis recanalization and resolution by targeting PTEN to regulate Akt/autophagy pathway and MMP2 expression. J Cell Mol Med 23(12):8493–8504

    Article  CAS  Google Scholar 

  2. Day ISCfWT (2014) Thrombosis: a major contributor to the global disease burden. J Thromb Haemost 12(10):1580–90

  3. Diaz JA, Ramacciotti E, Wakefield TW (2010) Do galectins play a role in venous thrombosis? A review. Thromb Res 125(5):373–376

    Article  CAS  Google Scholar 

  4. Ferreira T, Huber SC, de Moraes MB, Junior AL, Menezes FH, Orsi FA et al (2020) Low prevalence of post-thrombotic syndrome in patients treated with rivaroxaban. Vascul Pharmacol 124:106608

    Article  CAS  Google Scholar 

  5. Tapson VF, Humbert M (2006) Incidence and prevalence of chronic thromboembolic pulmonary hypertension: from acute to chronic pulmonary embolism. Proc Am Thorac Soc 3(7):564–567

    Article  Google Scholar 

  6. Pan Z, Zhang Y, Li C, Yin Y, Liu R, Zheng G, et al (2021) MiR-296-5p ameliorates deep venous thrombosis by inactivating S100A4. Exp Biol Med (Maywood), 15353702211023034

  7. Du X, Hong L, Sun L, Sang H, Qian A, Li W et al (2019) miR-21 induces endothelial progenitor cells proliferation and angiogenesis via targeting FASLG and is a potential prognostic marker in deep venous thrombosis. J Transl Med 17(1):270

    Article  Google Scholar 

  8. Jiang Z, Ma J, Wang Q, Wu F, Ping J, Ming L (2018) Combination of circulating miRNA-320a/b and D-dimer improves diagnostic accuracy in deep vein thrombosis patients. Med Sci Monit 24:2031–2037

    Article  CAS  Google Scholar 

  9. Qin J, Liang H, Shi D, Dai J, Xu Z, Chen D et al (2015) A panel of microRNAs as a new biomarkers for the detection of deep vein thrombosis. J Thromb Thrombolysis 39(2):215–221

    Article  CAS  Google Scholar 

  10. Meng Y, Yin Q, Ma Q, Qin H, Zhang J, Zhang B, et al (2021) FXII regulates the formation of deep vein thrombosis via the PI3K/AKT signaling pathway in mice. Int J Mol Med 47(5)

  11. Che P, Liu J, Shan Z, Wu R, Yao C, Cui J et al (2014) miR-125a-5p impairs endothelial cell angiogenesis in aging mice via RTEF-1 downregulation. Aging Cell 13(5):926–934

    Article  CAS  Google Scholar 

  12. Pan Q, Liao X, Liu H, Wang Y, Chen Y, Zhao B et al (2017) MicroRNA-125a-5p alleviates the deleterious effects of ox-LDL on multiple functions of human brain microvessel endothelial cells. Am J Physiol Cell Physiol 312(2):C119–C130

    Article  Google Scholar 

  13. Luo L, Xiao L, Lian G, Wang H, Xie L (2020) miR-125a-5p inhibits glycolysis by targeting hexokinase-II to improve pulmonary arterial hypertension. Aging (Albany NY) 12(10):9014–9030

    Article  CAS  Google Scholar 

  14. Jin QQ, Sun JH, Du QX, Lu XJ, Zhu XY, Fan HL et al (2017) Integrating microRNA and messenger RNA expression profiles in a rat model of deep vein thrombosis. Int J Mol Med 40(4):1019–1028

    Article  CAS  Google Scholar 

  15. Kasimu A, Apizi X, Talifujiang D, Ma X, Fang L, Zhou X (2021) miR-125a-5p in astrocytes attenuates peripheral neuropathy in type 2 diabetic mice through targeting TRAF6. Endocrinol Diabetes Nutr (Engl Ed)

  16. Yang C, Yang C, Huang Z, Zhang J, Chen N, Guo Y, et al (2021) Reduced expression of MiR-125a-5p aggravates LPS-induced experimental acute kidney injury pathology by targeting TRAF6. Life Sci 119657

  17. Min SK, Kim YH, Joh JH, Kang JM, Park UJ, Kim HK et al (2016) Diagnosis and treatment of lower extremity deep vein thrombosis: Korean practice guidelines. Vasc Specialist Int 32(3):77–104

    Article  Google Scholar 

  18. Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD et al (2012) Diagnosis of DVT: antithrombotic therapy and prevention of thrombosis, 9th ed: american college of chest physicians evidence-based clinical practice guidelines. Chest 141(2 Suppl):e351S-e418S

    Article  CAS  Google Scholar 

  19. Li HQ, Pan ZY, Yang Z, Zhang DB, Chen Q (2020) Overexpression of MicroRNA-122 resists oxidative stress-induced human umbilical vascular endothelial cell injury by inhibition of p53. Biomed Res Int 2020:9791608

    Google Scholar 

  20. Rabinovich A, Cohen JM, Cushman M, Kahn SR, Bio SOXI (2015) Association between inflammation biomarkers, anatomic extent of deep venous thrombosis, and venous symptoms after deep venous thrombosis. J Vasc Surg Venous Lymphat Disord. 3(4):347–53

  21. Huang H, Bhat A, Woodnutt G, Lappe R (2010) Targeting the ANGPT-TIE2 pathway in malignancy. Nat Rev Cancer 10(8):575–585

    Article  CAS  Google Scholar 

  22. Diao H, Xu X, Zhao B, Yang G (2021) miR135a5p inhibits tumor invasion by targeting ANGPT2 in gallbladder cancer. Mol Med Rep 24(1)

  23. Lu Z, Wang S, Zhu X, Yuan X, Zhan Y, Li Y et al (2019) Resveratrol induces endothelial progenitor cells angiogenesis via MiR-542-3p by targeting angiopoietin-2 and involves in recanalization of venous thrombosis. Med Sci Monit 25:7675–7683

    Article  CAS  Google Scholar 

  24. Hobohm L, Kolmel S, Niemann C, Kumpers P, Krieg VJ, Bochenek ML, et al (2021) Role of angiopoietin-2 in venous thrombus resolution and chronic thromboembolic disease. Eur Respir J

  25. Tuuminen R, Loukovaara S (2014) Increased intravitreal angiopoietin-2 levels in patients with retinal vein occlusion. Acta Ophthalmol 92(2):e164–e165

    Article  CAS  Google Scholar 

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No funding was received to assist with the preparation of this manuscript.

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Author notes

  1. Jianyuan Huang and Xinning Wu have equal contributions.

Authors and Affiliations

  1. General Surgery (Thyroid Gland/Blood Vessel), The First People’s Hospital of Neijiang, Neijiang, 641099, China

    Jianyuan Huang

  2. Department of Cardiovascular Medicine, People’s Hospital of Rizhao, Rizhao, 276827, China

    Xinning Wu

  3. Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College, No. 296, Kongtong East Road, Kongtong District, Pingliang, 744000, Gansu, China

    Quan Zhang, Lixia Yang, Guozhen Wan, Xiaoqiang Zhang & Ying Wang

  4. Department of Dermatological, Pingliang Traditional Chinese Medicine Hospital, Pingliang, 744000, Gansu, China

    Guannan Zhao

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  1. Jianyuan Huang
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  4. Lixia Yang
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Correspondence to Lixia Yang.

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Research Involving Human Participants

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Affiliated Hospital of Gansu Medical College.

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Huang, J., Wu, X., Zhang, Q. et al. Depleted miR-125a-5p Causes Vascular Endothelial Cell Dysfunction in Deep Vein Thrombosis by Targeting Angiopoietin 2. Indian J Hematol Blood Transfus 39, 116–122 (2023). https://doi.org/10.1007/s12288-022-01572-8

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  • DOI: https://doi.org/10.1007/s12288-022-01572-8

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