Influence of aspirin on the CX3CL1/CX3CR1 signaling pathway in acute pulmonary embolism

Zhang,Zhirong; Yang,Weiji; Ying,Rongbiao; Shi,Ying; Jiang,Huifang; Cai,Danli; Kuang,Jing; Yang,Ruhui; Wang,Lingcong

doi:10.3892/ijmm.2017.2969

Influence of aspirin on the CX3CL1/CX3CR1 signaling pathway in acute pulmonary embolism

Authors:
- Zhirong Zhang
- Weiji Yang
- Rongbiao Ying
- Ying Shi
- Huifang Jiang
- Danli Cai
- Jing Kuang
- Ruhui Yang
- Lingcong Wang
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Affiliations: Department of ICU, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China, Postgraduates Department of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, Department of Surgical Oncology, Tumor Hospital of Taizhou, Wenling, Zhejiang 317500, P.R. China, Department of Hematology, Tongde Hospital of Zhejiang, Hangzhou, Zhejiang 310012, P.R. China, College of Medicine and Health, Lishui University, Lishui, Zhejiang 323000, P.R. China
Published online on: April 26, 2017 https://doi.org/10.3892/ijmm.2017.2969
Pages: 1580-1588

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Abstract

The present study aimed to explore the influence of aspirin on the CX3CL1/CX3CR1 signaling pathway in acute pulmonary embolism (APE) in rats. Our previous study found that CX3CL1/CX3CR1 was increased in APE. However, the effect of this signaling pathway on APE remains unclear. CX3CL1-shRNA adenovirus and CX3CL1-overexpression vector were constructed. Male Sprague-Dawley rats were randomly divided into 9 groups (n=10): normal group (group N), sham operation group (group Sham), sham operation + aspirin group (group ASP), model group (group M), model + ASP group (group M+A), model + shRNA group (group M+SH), sham operation + CX3CL1-overexpression vector group (group Sham+Cx3), model + ASP + shRNA group (group M+A+SH), and model + ASP + CX3CL1-overexpression vector group (group M+A+CX3). Arterial pressure detection, hematoxylin and eosin staining, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and laser confocal scanning microscopy were applied. Aspirin significantly decreased pulmonary artery pressure, improve pathological changes in the embolism, and decreased the expression of CX3CL1/CX3CR1 and CX3CL1/NF-κB. Moreover, the adenovirus-overexpression CX3CL1 vector aggravated the inflammatory changes in APE, which were improved by aspirin. However, the intervention of the adenovirus CX3CL1 vector reduced the change, while its combination with aspirin significantly improved the change. In conclusion, aspirin improved pathological changes in rats with APE via the CX3CL1/CX3CR1 signaling pathway.

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1	Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR and Colwell CW: Prevention of venous thromboembolism: American college of chest physicians evidence-based clinical practice guidelines (8th edition). Chest. 133(Suppl 6): 381S–453S. 2008. View Article : Google Scholar : PubMed/NCBI
2	Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, Greer IA, Heit JA, Hutchinson JL, Kakkar AK, et al VTE Impact Assessment Group in Europe (VITAE): Venous thromboembolism (VTE) in Europe: The number of VTE events and associated morbidity and mortality. Thromb Haemost. 98:756–764. 2007.PubMed/NCBI
3	Yang Y, Liang L, Zhai Z, He H, Xie W, Peng X and Wang C; Investigators for National Cooperative Project for Prevention and Treatment of PTE-DVT: Pulmonary embolism incidence and fatality trends in chinese hospitals from 1997 to 2008: A multicenter registration study. PLoS One. 6:e268612011. View Article : Google Scholar : PubMed/NCBI
4	Wang L, Wu J, Zhang W, Zhi Y, Wu Y, Jiang R and Yang R: Effects of aspirin on the ERK and PI3K/Akt signaling pathways in rats with acute pulmonary embolism. Mol Med Rep. 8:1465–1471. 2013.PubMed/NCBI
5	Wang LC, Jiang RL, Zhang W, Wei LL and Yang RH: Effects of aspirin on the expression of nuclear factor-κB in a rat model of acute pulmonary embolism. World J Emerg Med. 5:229–233. 2014. View Article : Google Scholar
6	Wang LC, Wu JN, Xia GL, Mao W, Ying RB, Huang LQ and Jiang RL: Effect of aspirin on fractalkine in rats with pulmonary embolism. Trop J Pharm Res. 13:753–760. 2014. View Article : Google Scholar
7	Jiang R, Wei L, Zhu M, Wu J and Wang L: Aspirin inhibits LPS-induced expression of PI3K/Akt, ERK, NF-κB, CX3CL1, and MMPs in human bronchial epithelial cells. Inflammation. 39:643–650. 2016. View Article : Google Scholar
8	Konstantinides S, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galiè N, Gibbs J, Huisman M, Humbert M, Kucher N, et al; SEC Working Group for the ESC 2014 Guidelines on the Diagnosis and Management of Acute Pulmonary Embolism; Expert Reviewers for the ESC 2014 Guidelines on the Diagnosis and Management of Acute Pulmonary Embolism. SEC Clinical Practice Guidelines Committee: Comments on the 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism. Rev Esp Cardiol (Engl Ed). 68:10–16. 2015.
9	Schmeck J, Koch T, Patt B, Heller A, Neuhof H and van Ackern K: The role of endothelin-1 as a mediator of the pressure response after air embolism in blood perfused lungs. Intensive Care Med. 24:605–611. 1998. View Article : Google Scholar : PubMed/NCBI
10	Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A and Schall TJ: A new class of membrane-bound chemokine with a CX3C motif. Nature. 385:640–644. 1997. View Article : Google Scholar : PubMed/NCBI
11	Todorova D, Sabatier F, Doria E, Lyonnet L, Vacher Coponat H, Robert S, Despoix N, Legris T, Moal V, Loundou A, et al: Fractalkine expression induces endothelial progenitor cell lysis by natural killer cells. PLoS One. 6:e266632011. View Article : Google Scholar : PubMed/NCBI
12	Matsumiya T, Ota K, Imaizumi T, Yoshida H, Kimura H and Satoh K: Characterization of synergistic induction of CX3CL1/fractalkine by TNF-alpha and IFN-gamma in vascular endothelial cells: An essential role for TNF-alpha in post-transcriptional regulation of CX3CL1. J Immunol. 184:4205–4214. 2010. View Article : Google Scholar : PubMed/NCBI
13	Szukiewicz D, Kochanowski J, Mittal TK, Pyzlak M, Szewczyk G and Cendrowski K: CX3CL1 (fractalkine) and TNFα production by perfused human placental lobules under normoxic and hypoxic conditions in vitro: The importance of CX3CR1 signaling. Inflamm Res. 63:179–189. 2014. View Article : Google Scholar
14	Apostolakis S and Spandidos D: Chemokines and atherosclerosis: Focus on the CX3CL1/CX3CR1 pathway. Acta Pharmacol Sin. 34:1251–1256. 2013. View Article : Google Scholar : PubMed/NCBI
15	Ars C, Thurion P, Delos M, Sibille Y and Pilette C: Small airway obstruction in severe pulmonary arterial hypertension correlates with increased airway CD8⁺ T-cells and fractalkine expression. Eur Respir J. 34:1494–1496. 2009. View Article : Google Scholar : PubMed/NCBI
16	Ostrowski RP, Jadhav V, Chen W and Zhang JH: Reduced matrix metalloproteinase-9 activity and cell death after global ischemia in the brain preconditioned with hyperbaric oxygen. Acta Neurochir Suppl (Wien). 106:47–49. 2010. View Article : Google Scholar
17	Wang C, Zhai Z, Yang Y, Cheng Z, Ying K, Liang L, Dai H, Huang K, Lu W, et al: Inverse relationship of bleeding risk with clot burden during pulmonary embolism treatment with LMW heparin. Clin Respir J. 10:596–605. 2016. View Article : Google Scholar
18	Bhattacharyya S, Ghosh S and Sil PC: Amelioration of aspirin induced oxidative impairment and apoptotic cell death by a novel antioxidant protein molecule isolated from the herb Phyllanthus niruri. PLoS One. 9:e890262014. View Article : Google Scholar : PubMed/NCBI
19	Yamamoto Y and Gaynor RB: Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J Clin Invest. 107:135–142. 2001. View Article : Google Scholar : PubMed/NCBI
20	Szukiewicz D, Wojciechowska M, Bilska A, Stangret A, Szewczyk G, Mittal TK, Watroba M and Kochanowski J: Aspirin action in endothelial cells: Different patterns of response between chemokine CX3CL1/CX3CR1 and TNF-α/TNFR1 signaling pathways. Cardiovasc Drugs Ther. 29:219–229. 2015. View Article : Google Scholar : PubMed/NCBI
21	Guo Y, Apostalakis S, Blann AD and Lip GY: Plasma CX3CL1 levels and long term outcomes of patients with atrial fibrillation: The West Birmingham Atrial Fibrillation Project. Cerebrovasc Dis. 38:204–211. 2014. View Article : Google Scholar : PubMed/NCBI
22	Ogonda L, Hill J, Doran E, Dennison J, Stevenson M and Beverland D: Aspirin for thromboprophylaxis after primary lower limb arthroplasty: Early thromboembolic events and 90 day mortality in 11,459 patients. Bone Joint J. 98-B:341–348. 2016. View Article : Google Scholar : PubMed/NCBI
23	Braithwaite I, Dunbar L, Eathorne A, Weatherall M and Beasley R: Venous thromboembolism rates in patients with lower limb immobilization after Achilles tendon injury are unchanged after the introduction of prophylactic aspirin: Audit. J Thromb Haemost. 14:331–335. 2016. View Article : Google Scholar
24	Kaye ID, Patel DN, Strauss EJ, Alaia MJ, Garofolo G, Martinez A and Jazrawi LM: Prevention of venous thromboembolism after arthroscopic knee surgery in a low-risk population with the use of aspirin. A randomized trial. Bull Hosp Jt Dis (2013). 73:243–248. 2015.