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04.01.2021 | Original Article

Methotrexate Therapy Promotes Cell Coverage and Stability in in-Stent Neointima

verfasst von: Xianglan Liu, Ruoxi Zhang, Guosheng Fu, Yong Sun, Jian Wu, Maomao Zhang, Jinwei Tian, Xia Gu, Yang Zheng, Chengming Shi, Jingbo Hou, Bo Yu

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 5/2021

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Abstract

Purpose

Anti-proliferative drugs released from drug-eluting stents delay cell coverage and vascular healing, which increases the risk of late stent thrombosis. We assessed the potential effects of systemic methotrexate (MTX) on cell coverage, vascular healing and inflammation activation in vivo and in vitro.

Methods

We applied MTX in the right common carotid artery in a rabbit stenting model to determine the impact on cell coverage and inflammation activation using a serial optical coherence tomography (OCT) analysis and elucidated the molecular mechanism of MTX in human umbilical vein endothelial cells (HUVECs).

Results

Low-dose MTX promoted the development of cell coverage and vascular healing, which was associated with fewer uncovered struts (%) and cross-sections with any uncovered struts (%) at 4 weeks of stenting. The MTX group also exhibited lower rates of heterogeneity, microvessels and per-strut low-signal-intensity layers, indicating neointimal instability at 12 weeks of stenting. In vitro, low-dose MTX strongly inhibited HUVEC apoptosis, promoted proliferation and inhibited inflammatory activation by targeting the phosphoinositide 3-kinase (PI3K)/AKT signalling pathway.

Conclusion

Low-dose MTX may be a key means of promoting early cell coverage via the inhibition of the inflammatory response and stability of neointima by targeting inflammatory pathways after stent implantation.

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King SB 3rd., Smith SC Jr, Hirshfeld JW Jr, et al. 2007 focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. J Am Coll Cardiol. 2008;51:172–209.PubMedCrossRef

Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation. 2013;127:e6–245.PubMed

Ribichini F, Joner M, Ferrero V, et al. Effects of oral prednisone after stenting in a rabbit model of established atherosclerosis. J Am Coll Cardiol. 2007;50:176–85.PubMedCrossRef

Hou J, Qi H, Zhang M, et al. Development of lipid-rich plaque inside bare metal stent: possible mechanism of late stent thrombosis? An optical coherence tomography study. Heart. 2010;96:1187–90.PubMedCrossRef

Hu S, Wang C, Zhe C, et al. Plaque erosion delays vascular healing after drug eluting stent implantation in patients with acute coronary syndrome: an in vivo optical coherence tomography study. Catheter Cardiovasc Interv. 2017;89:592–600.PubMedCrossRef

Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685–95.PubMedCrossRef

Tunali-Akbay T, Sehirli O, Ercan F, Sener G. Resveratrol protects against methotrexate-induced hepatic injury in rats. J Pharm Pharm Sci. 2010;13:303–10.PubMedCrossRef

Ridker PM, Luscher TF. Anti-inflammatory therapies for cardiovascular disease. Eur Heart J. 2014;35:1782–91.PubMedPubMedCentralCrossRef

Zhang R, Chen S, Zhang H, et al. Effects of methotrexate in a rabbit model of in-stent neoatherosclerosis: an optical coherence tomography study. Sci Rep. 2016;6:33657.PubMedPubMedCentralCrossRef

10.

Sintek MA, Sparrow CT, Mikuls TR, et al. Repeat revascularisation outcomes after percutaneous coronary intervention in patients with rheumatoid arthritis. Heart. 2016;102:363–9.PubMedCrossRef

11.

Gouveia V, Oliveira DC, Tenorio E, Brito N, Sarinho E. Percutaneous coronary intervention: safety of methotrexate and its possible benefits on restenosis after bare-metal stent deployment. Cardiol Res. 2016;7:104–9.PubMedPubMedCentralCrossRef

12.

Hou J, Jia H, Liu H, et al. Neointimal tissue characteristics following sirolimus-eluting stent implantation: OCT quantitative tissue property analysis. Int J Cardiovasc Imaging. 2012;28:1879–86.PubMedCrossRef

13.

Kim JS, Hong MK, Shin DH, et al. Quantitative and qualitative changes in DES-related neointimal tissue based on serial OCT. JACC Cardiovasc Imaging. 2012;5:1147–55.PubMedCrossRef

14.

Inoue S, Koyama H, Miyata T, Shigematsu H. Cell replication induces in-stent lesion growth in rabbit carotid artery with preexisting intimal hyperplasia. Atherosclerosis. 2002;162:345–53.PubMedCrossRef

15.

Conaghan PG, Ostergaard M, Bowes MA, et al. Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques. Ann Rheum Dis. 2016;75:1024–33.PubMedCrossRef

16.

Prati F, Zimarino M, Stabile E, et al. Does optical coherence tomography identify arterial healing after stenting? An in vivo comparison with histology, in a rabbit carotid model. Heart. 2008;94:217–21.PubMedCrossRef

17.

Tian J, Hu S, Sun Y, et al. A novel model of atherosclerosis in rabbits using injury to arterial walls induced by ferric chloride as evaluated by optical coherence tomography as well as intravascular ultrasound and histology. J Biomed Biotechnol. 2012;2012:121867.PubMedPubMedCentralCrossRef

18.

Kang SJ, Mintz GS, Akasaka T, et al. Optical coherence tomographic analysis of in-stent neoatherosclerosis after drug-eluting stent implantation. Circulation. 2011;123:2954–63.PubMedCrossRef

19.

Nakazawa G, Otsuka F, Nakano M, et al. The pathology of neoatherosclerosis in human coronary implants bare-metal and drug-eluting stents. J Am Coll Cardiol. 2011;57:1314–22.PubMedPubMedCentralCrossRef

20.

Kim S, Kim JS, Shin DH, et al. Comparison of early strut coverage between zotarolimus- and everolimus-eluting stents using optical coherence tomography. Am J Cardiol. 2013;111:1–5.PubMedCrossRef

21.

Kornowski R, Hong MK, Tio FO, Bramwell O, Wu H, Leon MB. In-stent restenosis: contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J Am Coll Cardiol. 1998;31:224–30.PubMedCrossRef

22.

Chin-Quee SL, Hsu SH, Nguyen-Ehrenreich KL, et al. Endothelial cell recovery, acute thrombogenicity, and monocyte adhesion and activation on fluorinated copolymer and phosphorylcholine polymer stent coatings. Biomaterials. 2010;31:648–57.PubMedCrossRef

23.

Joner M, Nakazawa G, Finn AV, et al. Endothelial cell recovery between comparator polymer-based drug-eluting stents. J Am Coll Cardiol. 2008;52:333–42.PubMedCrossRef

24.

Miyake T, Ihara S, Miyake T, et al. Prevention of neointimal formation after angioplasty using nuclear factor-κB decoy oligodeoxynucleotide-coated balloon catheter in rabbit model. Circ Cardiovasc Interv. 2014;7:787–96.PubMedCrossRef

25.

Thornton CC, Al-Rashed F, Calay D, et al. Methotrexate-mediated activation of an AMPK-CREB-dependent pathway: a novel mechanism for vascular protection in chronic systemic inflammation. Ann Rheum Dis. 2016;75:439–48.PubMedCrossRef

26.

Leite AC Jr, Solano TV, Tavares ER, Maranhao RC. Use of combined chemotherapy with etoposide and methotrexate, both associated to lipid nanoemulsions for atherosclerosis treatment in cholesterol-fed rabbits. Cardiovasc Drugs Ther. 2015;29:15–22.PubMedCrossRef

27.

Aday AW, Ridker PM. Targeting residual inflammatory risk: a shifting paradigm for atherosclerotic disease. Front Cardiovasc Med. 2019;6:16.PubMedPubMedCentralCrossRef

28.

Kalkman DN, Aquino M, Claessen BE, et al. Residual inflammatory risk and the impact on clinical outcomes in patients after percutaneous coronary interventions. Eur Heart J. 2018;39:4101–8.PubMedCrossRef

29.

Micha R, Imamura F, Wyler von Ballmoos M, et al. Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol. 2011;108:1362–70.PubMedPubMedCentralCrossRef

30.

Roubille C, Richer V, Starnino T, et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2015;74:480–9.PubMedCrossRef

31.

Moreira DM, Lueneberg ME, da Silva RL, Fattah T, Gottschall CAM. Methotrexate therapy in ST-segment elevation myocardial infarctions: a randomized double-blind, placebo-controlled trial (TETHYS Trial). J Cardiovasc Pharmacol Ther. 2017;22:538–45.PubMedCrossRef

32.

Asanuma H, Sanada S, Ogai A, et al. Methotrexate and MX-68, a new derivative of methotrexate, limit infarct size via adenosine-dependent mechanisms in canine hearts. J Cardiovasc Pharmacol. 2004;43:574–9.PubMedCrossRef

33.

Yang X, Thomas DP, Zhang X, et al. Curcumin inhibits platelet-derived growth factor-stimulated vascular smooth muscle cell function and injury-induced neointima formation. Arterioscler Thromb Vasc Biol. 2006;26:85–90.PubMedCrossRef

34.

Otsuka F, Vorpahl M, Nakano M, et al. Pathology of second-generation everolimus-eluting stents versus first-generation sirolimus- and paclitaxel-eluting stents in humans. Circulation. 2014;129:211–23.PubMedCrossRef

35.

Finn AV, Joner M, Nakazawa G, et al. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation. 2007;115:2435–41.PubMedCrossRef

36.

Huang Y, Salu K, Liu X, et al. Methotrexate loaded SAE coated coronary stents reduce neointimal hyperplasia in a porcine coronary model. Heart. 2004;90:195–9.PubMedPubMedCentralCrossRef

37.

Chaabane C, Otsuka F, Virmani R, Bochaton-Piallat ML. Biological responses in stented arteries. Cardiovasc Res. 2013;99:353–63.PubMedCrossRef

38.

Wessels JA, Huizinga TW, Guchelaar HJ. Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis. Rheumatology (Oxford). 2008;47:249–55.CrossRef

39.

Holliday AC, Moody MN, Berlingeri-Ramos A. Methotrexate: role of treatment in skin disease. Skin Ther Lett. 2013;18:4–9.

40.

Corciulo C, Lendhey M, Wilder T, et al. Endogenous adenosine maintains cartilage homeostasis and exogenous adenosine inhibits osteoarthritis progression. Nat Commun. 2017;8:15019.PubMedPubMedCentralCrossRef

41.

Martelli AM, Tazzari PL, Evangelisti C, et al. Targeting the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin module for acute myelogenous leukemia therapy: from bench to bedside. Curr Med Chem. 2007;14:2009–23.PubMedCrossRef

42.

Shishodia S, Aggarwal BB. Nuclear factor-kappaB activation: a question of life or death. J Biochem Mol Biol. 2002;35:28–40.PubMed

43.

Aggarwal BB. Nuclear factor-kappaB: the enemy within. Cancer Cell. 2004;6:203–8.PubMedCrossRef

44.

Kim JS, Lee JH, Shin DH, et al. Long-term outcomes of neointimal hyperplasia without neoatherosclerosis after drug-eluting stent implantation. JACC Cardiovasc Imaging. 2014;7:788–95.PubMedCrossRef

Titel: Methotrexate Therapy Promotes Cell Coverage and Stability in in-Stent Neointima
verfasst von: Xianglan Liu
Ruoxi Zhang
Guosheng Fu
Yong Sun
Jian Wu
Maomao Zhang
Jinwei Tian
Xia Gu
Yang Zheng
Chengming Shi
Jingbo Hou
Bo Yu
Publikationsdatum: 04.01.2021
Verlag: Springer US
Erschienen in: Cardiovascular Drugs and Therapy / Ausgabe 5/2021
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-020-07121-7

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Methotrexate Therapy Promotes Cell Coverage and Stability in in-Stent Neointima