Skip to main content
Top
Published in: BMC Cardiovascular Disorders 1/2020

Open Access 01-12-2020 | Thrombosis | Research article

Role of miR-92a-3p, oxidative stress, and p38MAPK/NF-κB pathway in rats with central venous catheter related thrombosis

Authors: Xiao Gan, Huihan Zhao, Yan Wei, Qingjuan Jiang, Cui Wen, Yanping Ying

Published in: BMC Cardiovascular Disorders | Issue 1/2020

Login to get access

Abstract

Background

miR-92a-3p and oxidative stress are reportedly associated with venous thrombosis. However, the role of miR-92a-3p and oxidative stress in catheter-related thrombosis (CRT) remains ambiguous. Herein, we studied the roles of miR-92a-3p, oxidative stress, and p38-mitogen-activated protein kinase/nuclear factor kappa-B (MAPK/NF-κB) pathway in CRT.

Methods

Forty-five male rats were randomly and equally divided into control, sham operation, and CRT groups. The rats were sacrificed after 10 days. Reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) levels in the serum were determined by enzyme-linked immunosorbent assay (ELISA). The expression levels of miR-92a-3p, heme oxygenase-1 (HO-1), NF-κB p65, and p38 MAPK in the venous tissues were detected with quantitative polymerase chain reaction (qPCR) and Western blot.

Results

Thrombosis was observed only in the CRT group. Compared with the levels in the control and sham operation groups, ROS and MDA significantly increased in the CRT group, but SOD significantly decreased. qPCR and Western blot results showed that miR-92a-3p, HO-1, p38 MAPK, and NF-κB p65 expression was significantly upregulated in the venous tissues of the CRT group. Moreover, miR-92a-3p was positively correlated with HO-1, which was positively correlated with p38 MAPK and NF-κB p65.

Conclusion

miR-92a-3p was correlated with oxidative stress in CRT. miR-92a-3p and oxidative stress contributed to endothelial dysfunction and simultaneously was associated with CRT.
Literature
1.
go back to reference Rajasekhar A, Streiff MB. How I treat central venous access device-related upper extremity deep vein thrombosis. Blood. 2017;129(20):2727–36.CrossRef Rajasekhar A, Streiff MB. How I treat central venous access device-related upper extremity deep vein thrombosis. Blood. 2017;129(20):2727–36.CrossRef
2.
go back to reference Ullman AJ, Marsh N, Mihala G, Cooke M, Rickard CM. Complications of central venous access devices: a systematic review. Pediatrics. 2015;136(5):e1331–44.CrossRef Ullman AJ, Marsh N, Mihala G, Cooke M, Rickard CM. Complications of central venous access devices: a systematic review. Pediatrics. 2015;136(5):e1331–44.CrossRef
3.
go back to reference Thiyagarajah K, Ellingwood L, Endres K, Hegazi A, Radford J, Iansavitchene A, Lazo-Langner A. Post-thrombotic syndrome and recurrent thromboembolism in patients with upper extremity deep vein thrombosis: a systematic review and meta-analysis. Thromb Res. 2019;174:34–9.CrossRef Thiyagarajah K, Ellingwood L, Endres K, Hegazi A, Radford J, Iansavitchene A, Lazo-Langner A. Post-thrombotic syndrome and recurrent thromboembolism in patients with upper extremity deep vein thrombosis: a systematic review and meta-analysis. Thromb Res. 2019;174:34–9.CrossRef
4.
go back to reference Grant JD, Stevens SM, Woller SC, Lee EW, Kee ST, Liu DM, Lohan DG, Elliott CG. Diagnosis and management of upper extremity deep-vein thrombosis in adults. Thromb Haemost. 2012;108(6):1097–108.CrossRef Grant JD, Stevens SM, Woller SC, Lee EW, Kee ST, Liu DM, Lohan DG, Elliott CG. Diagnosis and management of upper extremity deep-vein thrombosis in adults. Thromb Haemost. 2012;108(6):1097–108.CrossRef
5.
go back to reference Chopra V, Anand S, Hickner A, Buist M, Rogers MA, Saint S, Flanders SA. Risk of venous thromboembolism associated with peripherally inserted central catheters: a systematic review and meta-analysis. Lancet. 2013;382(9889):311–25.CrossRef Chopra V, Anand S, Hickner A, Buist M, Rogers MA, Saint S, Flanders SA. Risk of venous thromboembolism associated with peripherally inserted central catheters: a systematic review and meta-analysis. Lancet. 2013;382(9889):311–25.CrossRef
6.
go back to reference Geerts W. Central venous catheter-related thrombosis. Hematol Am Soc Hematol Educ Program. 2014;2014(1):306–11.CrossRef Geerts W. Central venous catheter-related thrombosis. Hematol Am Soc Hematol Educ Program. 2014;2014(1):306–11.CrossRef
7.
go back to reference Sogaard KK, Schmidt M, Pedersen L, Horvath-Puho E, Sorensen HT. 30-year mortality after venous thromboembolism: a population-based cohort study. Circulation. 2014;130(10):829–36.CrossRef Sogaard KK, Schmidt M, Pedersen L, Horvath-Puho E, Sorensen HT. 30-year mortality after venous thromboembolism: a population-based cohort study. Circulation. 2014;130(10):829–36.CrossRef
8.
go back to reference Ostlund A, Flaring U, Norberg A, Dahlberg A, Berner J, Kaiser S, Vermin L, Svenningsson A, Frisk T, Larsson P, et al. Incidence of and risk factors for venous thrombosis in children with percutaneous non-tunnelled central venous catheters. Br J Anaesth. 2019;123(3):316–24.CrossRef Ostlund A, Flaring U, Norberg A, Dahlberg A, Berner J, Kaiser S, Vermin L, Svenningsson A, Frisk T, Larsson P, et al. Incidence of and risk factors for venous thrombosis in children with percutaneous non-tunnelled central venous catheters. Br J Anaesth. 2019;123(3):316–24.CrossRef
9.
go back to reference Gareri C, De Rosa S, Indolfi C. MicroRNAs for restenosis and thrombosis after vascular injury. Circ Res. 2016;118(7):1170–84.CrossRef Gareri C, De Rosa S, Indolfi C. MicroRNAs for restenosis and thrombosis after vascular injury. Circ Res. 2016;118(7):1170–84.CrossRef
10.
go back to reference Chamorro-Jorganes A, Lee MY, Araldi E, Landskroner-Eiger S, Fernandez-Fuertes M, Sahraei M, Quiles Del Rey M, van Solingen C, Yu J, Fernandez-Hernando C, et al. VEGF-induced expression of miR-17-92 cluster in endothelial cells is mediated by ERK/ELK1 activation and regulates angiogenesis. Circ Res. 2016;118(1):38–47.CrossRef Chamorro-Jorganes A, Lee MY, Araldi E, Landskroner-Eiger S, Fernandez-Fuertes M, Sahraei M, Quiles Del Rey M, van Solingen C, Yu J, Fernandez-Hernando C, et al. VEGF-induced expression of miR-17-92 cluster in endothelial cells is mediated by ERK/ELK1 activation and regulates angiogenesis. Circ Res. 2016;118(1):38–47.CrossRef
11.
go back to reference Fiedler J, Thum T. New insights into miR-17-92 cluster regulation and angiogenesis. Circ Res. 2016;118(1):9–11.CrossRef Fiedler J, Thum T. New insights into miR-17-92 cluster regulation and angiogenesis. Circ Res. 2016;118(1):9–11.CrossRef
12.
go back to reference Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, Burchfield J, Fox H, Doebele C, Ohtani K, et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science. 2009;324(5935):1710–3.CrossRef Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, Burchfield J, Fox H, Doebele C, Ohtani K, et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science. 2009;324(5935):1710–3.CrossRef
13.
go back to reference Chen Z, Wen L, Martin M, Hsu CY, Fang L, Lin FM, Lin TY, Geary MJ, Geary GG, Zhao Y, et al. Oxidative stress activates endothelial innate immunity via sterol regulatory element binding protein 2 (SREBP2) transactivation of microRNA-92a. Circulation. 2015;131(9):805–14.CrossRef Chen Z, Wen L, Martin M, Hsu CY, Fang L, Lin FM, Lin TY, Geary MJ, Geary GG, Zhao Y, et al. Oxidative stress activates endothelial innate immunity via sterol regulatory element binding protein 2 (SREBP2) transactivation of microRNA-92a. Circulation. 2015;131(9):805–14.CrossRef
14.
go back to reference Fan ZX, Yang J. The role of microRNAs in regulating myocardial ischemia reperfusion injury. Saudi Med J. 2015;36(7):787–93.CrossRef Fan ZX, Yang J. The role of microRNAs in regulating myocardial ischemia reperfusion injury. Saudi Med J. 2015;36(7):787–93.CrossRef
15.
go back to reference Jin QQ, Sun JH, Du QX, Lu XJ, Zhu XY, Fan HL, Holscher C, Wang YY. Integrating microRNA and messenger RNA expression profiles in a rat model of deep vein thrombosis. Int J Mol Med. 2017;40(4):1019–28.CrossRef Jin QQ, Sun JH, Du QX, Lu XJ, Zhu XY, Fan HL, Holscher C, Wang YY. Integrating microRNA and messenger RNA expression profiles in a rat model of deep vein thrombosis. Int J Mol Med. 2017;40(4):1019–28.CrossRef
16.
go back to reference Nifong TP, McDevitt TJ. The effect of catheter to vein ratio on blood flow rates in a simulated model of peripherally inserted central venous catheters. Chest. 2011;140(1):48–53.CrossRef Nifong TP, McDevitt TJ. The effect of catheter to vein ratio on blood flow rates in a simulated model of peripherally inserted central venous catheters. Chest. 2011;140(1):48–53.CrossRef
17.
go back to reference Sinha N, Dabla PK. Oxidative stress and antioxidants in hypertension-a current review. Curr Hypertens Rev. 2015;11(2):132–42.CrossRef Sinha N, Dabla PK. Oxidative stress and antioxidants in hypertension-a current review. Curr Hypertens Rev. 2015;11(2):132–42.CrossRef
18.
go back to reference Montezano AC, Dulak-Lis M, Tsiropoulou S, Harvey A, Briones AM, Touyz RM. Oxidative stress and human hypertension: vascular mechanisms, biomarkers, and novel therapies. Can J Cardiol. 2015;31(5):631–41.CrossRef Montezano AC, Dulak-Lis M, Tsiropoulou S, Harvey A, Briones AM, Touyz RM. Oxidative stress and human hypertension: vascular mechanisms, biomarkers, and novel therapies. Can J Cardiol. 2015;31(5):631–41.CrossRef
19.
go back to reference Liu H, Wu HY, Wang WY, Zhao ZL, Liu XY, Wang LY. Regulation of miR-92a on vascular endothelial aging via mediating Nrf2-KEAP1-ARE signal pathway. Eur Rev Med Pharmacol Sci. 2017;21(11):2734–42.PubMed Liu H, Wu HY, Wang WY, Zhao ZL, Liu XY, Wang LY. Regulation of miR-92a on vascular endothelial aging via mediating Nrf2-KEAP1-ARE signal pathway. Eur Rev Med Pharmacol Sci. 2017;21(11):2734–42.PubMed
20.
go back to reference Gou L, Zhao L, Song W, Wang L, Liu J, Zhang H, Huang Y, Lau CW, Yao X, Tian XY, et al. Inhibition of miR-92a suppresses oxidative stress and improves endothelial function by Upregulating Heme Oxygenase-1 in db/db mice. Antioxid Redox Signal. 2018;28(5):358–70.CrossRef Gou L, Zhao L, Song W, Wang L, Liu J, Zhang H, Huang Y, Lau CW, Yao X, Tian XY, et al. Inhibition of miR-92a suppresses oxidative stress and improves endothelial function by Upregulating Heme Oxygenase-1 in db/db mice. Antioxid Redox Signal. 2018;28(5):358–70.CrossRef
21.
go back to reference Lou ZK. The mechanism research of SIRT1 protecting endothelial cells from oxidative damage and inhibiting expression of pro-thrombosis molecules in deep venous thrombosis. Dissertation. Yunnan Province: Kuming Medical University; 2016. Lou ZK. The mechanism research of SIRT1 protecting endothelial cells from oxidative damage and inhibiting expression of pro-thrombosis molecules in deep venous thrombosis. Dissertation. Yunnan Province: Kuming Medical University; 2016.
22.
go back to reference Fan H, Wu PF, Zhang L, Hu ZL, Wang W, Guan XL, Luo H, Ni M, Yang JW, Li MX, et al. Methionine sulfoxide reductase a negatively controls microglia-mediated neuroinflammation via inhibiting ROS/MAPKs/NF-kappaB signaling pathways through a catalytic antioxidant function. Antioxid Redox Signal. 2015;22(10):832–47.CrossRef Fan H, Wu PF, Zhang L, Hu ZL, Wang W, Guan XL, Luo H, Ni M, Yang JW, Li MX, et al. Methionine sulfoxide reductase a negatively controls microglia-mediated neuroinflammation via inhibiting ROS/MAPKs/NF-kappaB signaling pathways through a catalytic antioxidant function. Antioxid Redox Signal. 2015;22(10):832–47.CrossRef
23.
go back to reference Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, Kearon C, Schunemann HJ, Crowther M, Pauker SG, et al. Diagnosis of DVT: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e351S–418S.CrossRef Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, Kearon C, Schunemann HJ, Crowther M, Pauker SG, et al. Diagnosis of DVT: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e351S–418S.CrossRef
24.
go back to reference Evans RS, Sharp JH, Linford LH, Lloyd JF, Woller SC, Stevens SM, Elliott CG, Tripp JS, Jones SS, Weaver LK. Reduction of peripherally inserted central catheter-associated DVT. Chest. 2013;143(3):627–33.CrossRef Evans RS, Sharp JH, Linford LH, Lloyd JF, Woller SC, Stevens SM, Elliott CG, Tripp JS, Jones SS, Weaver LK. Reduction of peripherally inserted central catheter-associated DVT. Chest. 2013;143(3):627–33.CrossRef
25.
go back to reference Sharp R, Cummings M, Fielder A, Mikocka-Walus A, Grech C, Esterman A. The catheter to vein ratio and rates of symptomatic venous thromboembolism in patients with a peripherally inserted central catheter (PICC): a prospective cohort study. Int J Nurs Stud. 2015;52(3):677–85.CrossRef Sharp R, Cummings M, Fielder A, Mikocka-Walus A, Grech C, Esterman A. The catheter to vein ratio and rates of symptomatic venous thromboembolism in patients with a peripherally inserted central catheter (PICC): a prospective cohort study. Int J Nurs Stud. 2015;52(3):677–85.CrossRef
26.
go back to reference De Luca T, Szilagyi KL, Hargreaves KA, Collins KS, Benson EA. Improving the patency of jugular vein catheters in Sprague-Dawley rats by using an antiseptic nitrocellulose coating. J Am Assoc Lab Anim Sci. 2018;57(5):520–8.CrossRef De Luca T, Szilagyi KL, Hargreaves KA, Collins KS, Benson EA. Improving the patency of jugular vein catheters in Sprague-Dawley rats by using an antiseptic nitrocellulose coating. J Am Assoc Lab Anim Sci. 2018;57(5):520–8.CrossRef
27.
go back to reference Quenot JP, Helms J, Bourredjem A, Dargent A, Meziani F, Badie J, Blasco G, Piton G, Capellier G, Mezher C, et al. Trisodium citrate 4% versus heparin as a catheter lock for non-tunneled hemodialysis catheters in critically ill patients: a multicenter, randomized clinical trial. Ann Intensive Care. 2019;9(1):75.CrossRef Quenot JP, Helms J, Bourredjem A, Dargent A, Meziani F, Badie J, Blasco G, Piton G, Capellier G, Mezher C, et al. Trisodium citrate 4% versus heparin as a catheter lock for non-tunneled hemodialysis catheters in critically ill patients: a multicenter, randomized clinical trial. Ann Intensive Care. 2019;9(1):75.CrossRef
28.
go back to reference Diamond CE, Hennessey C, Meldau J, Guelcher CJ, Guerrera MF, Conklin LS, Sharma KV, Diab YA. Catheter-related venous thrombosis in hospitalized pediatric patients with inflammatory bowel disease: incidence, characteristics, and role of anticoagulant Thromboprophylaxis with enoxaparin. J Pediatr. 2018;198:53–9.CrossRef Diamond CE, Hennessey C, Meldau J, Guelcher CJ, Guerrera MF, Conklin LS, Sharma KV, Diab YA. Catheter-related venous thrombosis in hospitalized pediatric patients with inflammatory bowel disease: incidence, characteristics, and role of anticoagulant Thromboprophylaxis with enoxaparin. J Pediatr. 2018;198:53–9.CrossRef
29.
go back to reference Liu K, Zhou Y, Xie W, Gu Z, Jin Y, Ye X, Chen X, Fan B, Wang H, Cui Y. Handgrip exercise reduces peripherally-inserted central catheter-related venous thrombosis in patients with solid cancers: a randomized controlled trial. Int J Nurs Stud. 2018;86:99–106.CrossRef Liu K, Zhou Y, Xie W, Gu Z, Jin Y, Ye X, Chen X, Fan B, Wang H, Cui Y. Handgrip exercise reduces peripherally-inserted central catheter-related venous thrombosis in patients with solid cancers: a randomized controlled trial. Int J Nurs Stud. 2018;86:99–106.CrossRef
30.
go back to reference Maegdefessel L, Rayner KJ, Leeper NJ. MicroRNA regulation of vascular smooth muscle function and phenotype: early career committee contribution. Arterioscler Thromb Vasc Biol. 2015;35(1):2–6.CrossRef Maegdefessel L, Rayner KJ, Leeper NJ. MicroRNA regulation of vascular smooth muscle function and phenotype: early career committee contribution. Arterioscler Thromb Vasc Biol. 2015;35(1):2–6.CrossRef
31.
go back to reference Williams TP, Shaw S, Porter A, Berkwitt L. Aortic thrombosis in dogs. J Vet Emerg Crit Care (San Antonio). 2017;27(1):9–22.CrossRef Williams TP, Shaw S, Porter A, Berkwitt L. Aortic thrombosis in dogs. J Vet Emerg Crit Care (San Antonio). 2017;27(1):9–22.CrossRef
32.
go back to reference Wang LH, Wei F, Jia L, Lu Z, Wang B, Dong HY, Yu HB, Sun GJ, Yang J, Li B, et al. Fibrin sheath formation and intimal thickening after catheter placement in dog model: role of hemodynamic wall shear stress. J Vasc Access. 2015;16(4):275–84.CrossRef Wang LH, Wei F, Jia L, Lu Z, Wang B, Dong HY, Yu HB, Sun GJ, Yang J, Li B, et al. Fibrin sheath formation and intimal thickening after catheter placement in dog model: role of hemodynamic wall shear stress. J Vasc Access. 2015;16(4):275–84.CrossRef
33.
go back to reference Terry CM, He Y, Cheung AK. Rivaroxaban improves patency and decreases inflammation in a mouse model of catheter thrombosis. Thromb Res. 2016;144:106–12.CrossRef Terry CM, He Y, Cheung AK. Rivaroxaban improves patency and decreases inflammation in a mouse model of catheter thrombosis. Thromb Res. 2016;144:106–12.CrossRef
34.
go back to reference Boon RA, Hergenreider E, Dimmeler S. Atheroprotective mechanisms of shear stress-regulated microRNAs. Thromb Haemost. 2012;108(4):616–20.CrossRef Boon RA, Hergenreider E, Dimmeler S. Atheroprotective mechanisms of shear stress-regulated microRNAs. Thromb Haemost. 2012;108(4):616–20.CrossRef
35.
go back to reference Loyer X, Potteaux S, Vion AC, Guerin CL, Boulkroun S, Rautou PE, Ramkhelawon B, Esposito B, Dalloz M, Paul JL, et al. Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice. Circ Res. 2014;114(3):434–43.CrossRef Loyer X, Potteaux S, Vion AC, Guerin CL, Boulkroun S, Rautou PE, Ramkhelawon B, Esposito B, Dalloz M, Paul JL, et al. Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice. Circ Res. 2014;114(3):434–43.CrossRef
36.
go back to reference Alam J, Cook JL. How many transcription factors does it take to turn on the heme oxygenase-1 gene? Am J Respir Cell Mol Biol. 2007;36(2):166–74.CrossRef Alam J, Cook JL. How many transcription factors does it take to turn on the heme oxygenase-1 gene? Am J Respir Cell Mol Biol. 2007;36(2):166–74.CrossRef
37.
go back to reference Paine A, Eiz-Vesper B, Blasczyk R, Immenschuh S. Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential. Biochem Pharmacol. 2010;80(12):1895–903.CrossRef Paine A, Eiz-Vesper B, Blasczyk R, Immenschuh S. Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential. Biochem Pharmacol. 2010;80(12):1895–903.CrossRef
38.
go back to reference Calay D, Mason JC. The multifunctional role and therapeutic potential of HO-1 in the vascular endothelium. Antioxid Redox Signal. 2014;20(11):1789–809.CrossRef Calay D, Mason JC. The multifunctional role and therapeutic potential of HO-1 in the vascular endothelium. Antioxid Redox Signal. 2014;20(11):1789–809.CrossRef
Metadata
Title
Role of miR-92a-3p, oxidative stress, and p38MAPK/NF-κB pathway in rats with central venous catheter related thrombosis
Authors
Xiao Gan
Huihan Zhao
Yan Wei
Qingjuan Jiang
Cui Wen
Yanping Ying
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2020
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-020-01436-x

Other articles of this Issue 1/2020

BMC Cardiovascular Disorders 1/2020 Go to the issue