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Markers of the Development of the Reconstruction Area Restenosis After Endovascular Interventions in Lower Limbs Arteries

https://doi.org/10.23934/2223-9022-2021-10-4-669-675

Abstract

Restenosis of the reconstruction zone is one of the main postoperative complications of vascular reconstructions, which develops in 18–40% of cases and leads to an increase in the risk of limb loss to 20–25%. The search for new markers for predicting the development of this complication is an urgent problem today.

Aim of study. To assess the dynamics of markers of apoptosis and cell proliferation at different times after endovascular intervention and their role in the development of restenosis of the reconstruction zone in patients with peripheral arterial disease (PAD).

Material and methods. The clinical study included 30 patients with PAD stage III disease. After further examination, the patients underwent endovascular intervention on the arteries of the femoral-popliteal segment. If restenosis developed, the patients were re-operated. In patients before surgery, within the first hour, and then on days 1, 7, 14, 21, 30 after the operation, venous blood was taken to determine the markers Bax, sFas, PDGF BB using enzyme immunoassay.

Results. After endovascular intervention, the first wave of apoptosis was triggered with an increase in the amount of proapoptotic protein Bax (p=0,00003) from 1 to 24 hours, followed by a decrease by day 7 (p=0.0008) compared to the amount on day 1. The PDGF BB level increased from day 1 after surgery (p=0.03) with maximum values on day 7 (p=0.0002) compared to the level on day 1. Then the second wave was triggered with a peak decrease in the level of the apoptosis inhibitor sFas on day 21 (p=0.002). After 9-12 months, restenosis of the intervention zone with a return of limb ischemia developed in 10 patients. During the first hour (p=0.004) in patients with restenosis, the level of Bax protein was significantly increased, with an increase in the level of PDGF BB by day 7 (p=0.011), and sFas by day 21 (p=0.0001), PDGF BB by the end of 1 month (p=0.004) compared to values in patients without this complication.

Conclusion. 1. Endovascular intervention causes two waves of apoptosis in the postoperative period. The first wave is associated with an increase in Bax protein in the first hours, followed by an increase in PDGF BB on day 7. The second wave of apoptosis is due to a decrease in the inhibitor of apoptosis — sFas for 21 days against the background of the shift of the PDGF BB to the initial level. 2. An increase in Bax protein within the first hours after surgery in the course of PDGF BB growth on day 7 with an increased amount of sFas on day 21 leads and PDGF BB by the end of 1 month leads to the development of restenosis of the intervention area. 

About the Authors

R. E. Kalinin
I.P. Pavlov Ryazan State Medical University of Ministry of Health of the Russian Federation
Russian Federation

Doctor of Medical Sciences, Professor, Head of the Department of Cardiovascular, X-ray Endovascular, Operative Surgery
and Topographic Anatomy,

9 Vysokovoltnaya St., Ryazan, 390026



I. A. Suchkov
I.P. Pavlov Ryazan State Medical University of Ministry of Health of the Russian Federation
Russian Federation

Doctor of Medical Sciences, Professor, Professor of the Department of Cardiovascular, X-ray Endovascular, Operative
Surgery and Topographic Anatomy,

9 Vysokovoltnaya St., Ryazan, 390026



E. A. Klimentova
I.P. Pavlov Ryazan State Medical University of Ministry of Health of the Russian Federation
Russian Federation

Candidate of Medical Sciences, Applicant of the Department of Cardiovascular, X-ray Endovascular, Operative Surgery and
Topographic Anatomy,

9 Vysokovoltnaya St., Ryazan, 390026



A. V. Shchulkin
I.P. Pavlov Ryazan State Medical University of Ministry of Health of the Russian Federation
Russian Federation

Doctor of Medical Sciences, Professor of the Department of Pharmacology with a course in Pharmacy at the Faculty of
Additional Professional Education,

9 Vysokovoltnaya St., Ryazan, 390026



References

1. Gökgöl C, Diehm N, Räber L, Büchler P. Prediction of restenosis based on hemodynamical markers in revascularized femoro-popliteal arteries during leg flexion. Biomech Model Mechanobiol. 2019;18(6):1883–1893. PMID: 31197509 https://doi.org/10.1007/s10237-019-01183-9

2. Fang J, Pan Z, Guo X. Research advance of ANRIL on atherosclerosis by regulating cell proliferation and apoptosis. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020;25;49(1):113–117. PMID: 32621415

3. Rymer JA, Jones WS. Femoropopliteal In-Stent Restenosis. Circ Cardiovasc Interv. 2018;11(12):e007559. PMID: 30562092 https://doi/org/10.1161/CIRCINTERVENTIONS.118.007559

4. Zhu ZR, He Q, Wu WB, Chang G, Yao C, Zhao Y, et al. MiR-140-3p is Involved in In-Stent Restenosis by Targeting C-Myb and BCL-2 in Peripheral Artery Disease. J Atheroscler Thromb. 2018;25(11):1168– 1181. PMID: 29760303 https://doi.org/10.5551/jat.44024

5. Kalinin RE, Suchkov IA, Klimentova EA, Egorov AA. To the Question of the Role of Apoptosis in the Development of Atherosclerosis and Restenosis of the Reconstruction Zone. Novosti khirurgii. 2020;28(4):418–427. (In Russ.) https://doi.org/10.18484/2305-0047.2020.4.418

6. Klimentova EA, Suchkov IA, Egorov AA, Kalinin RE. Apoptosis and Cell Proliferation Markers in Inflammatory-Fibroproliferative Diseases of the Vessel Wall (Review). Sovremennye tehnologii v medicine. 2020;12(4):119–128. https://doi.org/10.17691/stm2020.12.4.13

7. Jiang C, Yang YF, Cheng SH. Fas ligand gene therapy for vascular intimal hyperplasia. Curr Gene Ther. 2004;4(1):33–39. PMID: 15032612 https://doi.org/10.2174/1566523044578022/

8. Su G, Sun G, Liu H, Shu L, Liang Z. Downregulation of miR-34a promotes endothelial cell growth and suppresses apoptosis in atherosclerosis by regulating Bcl-2. Heart Vessels. 2018;33(10):1185–1194. PMID: 29704100. https://doi.org/10.1007/s00380-018-1169-7

9. Walsh K, Smith RC, Kim HS. Vascular cell apoptosis in remodeling, restenosis, and plaque rupture. Circ Res. 2000;87(3):184–188. PMID: 10926867. https://doi.org/10.1161/01.res.87.3.184

10. Lu QB, Wan MY, Wang PY, Zhang CX, Xu DY, Liao X, et al. Chicoric acid prevents PDGF-BB-induced VSMC dedifferentiation, proliferation and migration by suppressing ROS/NFкB/mTOR/P70S6K signaling cascade. Redox Biol. 2018;14:656–668. PMID: 29175753 https://doi.org/10.1016/j.redox.2017.11.012

11. Rutherford C, Martin W, Salame M, Carrier M, Anggård E, Ferns G. Substantial inhibition of neointimal response to balloon injury in the rat carotid artery using a combination of antibodies to platelet-derived growth factor-BB and basic fibroblast growth factor. Atherosclerosis. 1997;130(1-2):45–51. PMID: 9126647 https://doi.org/10.1016/s0021-9150(96)06042-x

12. Bokeriya LA, Pokrovskiy AV. Natsional’nye rekomendatsii po diagnostike i lecheniyu zabolevaniyu arteriy nizhnikh konechnostey. Moscow; 2019. (in Russ.) Available at: http://www.angiolsurgery.org/library/recommendations/2019/recommendations_LLA_2019.pdf [Accessed Nov 23, 2021]

13. Kalinin RE, Suchkov IA, Klimentova ЕA, Egorov AA, Povarov VO. Apoptosis in vascular pathology: present and future. I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):79–87. (in Russ.) https://doi.org/10.23888/PAVLOVJ202028179-87

14. Walsh K, Smith RC, Kim HS. Vascular cell apoptosis in remodeling, restenosis, and plaque rupture. Circ Res. 2000;87(3):184–188. PMID: 10926867 https://doi.org/10.1161/01.res.87.3.184

15. Clowes AW, Reidy MA, Clowes MM. Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium. Lab Invest. 1983;49(3):327–333. PMID: 6887785

16. Bochaton-Piallat M, Gabbiani F, Redard M, Desmouliere A, Gabbiani G. Apoptosis participates in cellularity regulation during rat aortic intimal thickening. Am J Pathol. 1995; 146(5):1059–1064. PMID: 7747800

17. Katsaros KM, Wiesbauer F, Speidl WS, Kastl SP, Huber K, Zorn G, et al. High soluble Fas and soluble Fas Ligand serum levels before stent implantation are protective against restenosis. Thromb Haemost. 2011;105(5):883–891. PMID: 21359408 https://doi.org/10.1160/TH10- 09-0566

18. Strelnikova EA, Trushkina PYu, Surov IYu, Korotkova NV, Mzhvanadze ND, Deev RV. Endothelium in Vivo And in Vitro. Part 1: Histogenesis, Structure, Cytophysiology and Key Markers. Eruditio Juvenium. 2019;7(3):450–465. (in Russ). https://doi.org/10.23888/HMJ201973450-465

19. Guégan JP, Legembre P. Nonapoptotic functions of Fas/CD95 in the immune response. FEBS J. 2018;285(5):809–827. PMID: 29032605 https://doi.org/10.1111/febs.1429


Review

For citations:


Kalinin R.E., Suchkov I.A., Klimentova E.A., Shchulkin A.V. Markers of the Development of the Reconstruction Area Restenosis After Endovascular Interventions in Lower Limbs Arteries. Russian Sklifosovsky Journal "Emergency Medical Care". 2021;10(4):669-675. https://doi.org/10.23934/2223-9022-2021-10-4-669-675

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ISSN 2223-9022 (Print)
ISSN 2541-8017 (Online)