Today: Dec 22, 2024
RU / EN
Last update: Oct 30, 2024
Expression of Apoptotic Markers Bcl-2 and Bax in the Vascular Wall

Expression of Apoptotic Markers Bcl-2 and Bax in the Vascular Wall

Klimentova E.A., Suchkov I.A., Shchulkin A.V., Glazkova A.P., Kalinin R.E.
Key words: atherosclerotic plaque; apoptotic proteins; Bax and Bcl-2 proteins; lower limb arterial atherosclerosis; cholesterol.
2021, volume 13, issue 2, page 46.

Full text

html pdf
1255
1506

The aim of the study was to assess the levels of Всl-2 and Bax proteins in the vascular wall and their correlation with serum cholesterol in patients with stage III–IV atherosclerosis obliterans of lower limb arteries.

Materials and Methods. The study included 32 patients with stage III–IV atherosclerosis obliterans of the lower limb. Samples of intraoperative material (all three layers of the vascular wall) including an atherosclerotic plaque (AP) were taken during primary open surgery on major leg arteries. As a control, we used samples of the arterial wall without visible signs of atherosclerosis. Based on AP ultrasonography, the patients were divided into two groups: with APs of mixed echogenicity and with hyperechoic (calcified) AP. The vascular samples were crushed and homogenized for further measurements of Всl-2 and Bax proteins; in a separate setup, cholesterol in blood serum was measured.

Results. In patients without atherosclerotic changes, the level of the anti-apoptotic protein Bcl-2 in the arterial wall was 1.25 ng/mg, and that of the pro-apoptotic protein Bax — 4.7 ng/mg. In the case of APs of mixed echogenicity, the expression of Bcl-2 was 1.8 ng/mg (p=0.143) and that of Bax — 5.1 ng/mg (p=0.834), with no significant differences from AP-free vascular wall samples. In the arterial wall containing a heterogeneous calcified AP, the expression of Bcl-2 was 0.9 ng/mg (p=0.143), In contrast, the level of Bax was 6.8 ng/mg, which showed its significant increase as compared with the non-AP controls (p=0.02). In the cases with predominantly hyperechoic AP, the expression of Bcl-2 was significantly lower (p=0.036), and that of Bax — significantly higher (p=0.036) in comparison with AP of mixed echogenicity. In patients with hyperechoic AP, we found a negative correlation between the Bax and Bcl-2 values (r=–0.315) and a positive correlation between the Bax expression and serum cholesterol (r=0.617).

Conclusion. In arterial walls with hyperechoic (calcified) APs, the expression of anti-apoptotic protein Bcl-2 is reduced, and that of pro-apoptotic protein Bax is increased, which indicates the apoptosis activation in advanced atherosclerotic lesions. In patients with such APs, elevated cholesterol levels directly correlate with the increased expression of pro-apoptotic Bax protein (r=0.617).

  1. Marchenko A.V., Vronskiy A.S., Myalyuk P.A., Kamenskikh M.S. Historical aspects and the current state of treatment of combined coronary and carotid artery disease. Kompleksnye problemy serdečno-sosudistyh zabolevanij 2020; 9(1): 74–81.
  2. Strelnikova E.A., Trushkina P.Yu., Surov I.Yu., Korotkova N.V., Mzhavanadze N.D., Deev R.V. Endothelium in vivo and in vitro. Part 1: histogenesis, structure, cytophysiology and key markers. Nauka molodykh (Eruditio Juvenium) 2019; 7(3): 450–465, https://doi.org/10.23888/hmj201973450-465.
  3. Kalinin R.E., Suchkov I.A., Mzhavanadze N.D., Demikhov V.G., Zhurina O.N., Klimentova E.A. Hemostatic changes in patients with peripheral artery disease before and after bypass surgery. Khirurgiya. Zhurnal imeni N.I. Pirogova 2018; 8: 46–49, https://doi.org/10.17116/hirurgia2018846.
  4. Pshennikov A.S., Deev R.V. Morphological illustration of alterations in the arterial endothelium in ischemic and reperfusion injuries. Rossijskij mediko-biologiceskij vestnik imeni akademika I.P. Pavlova 2018; 26(2): 184–194.
  5. Paone S., Baxter A.A., Hulett M.D., Poon I.K.H. Endothelial cell apoptosis and the role of endothelial cell-derived extracellular vesicles in the progression of atherosclerosis. Cell Mol Life Sci 2019; 76(6): 1093–1106, https://doi.org/10.1007/s00018-018-2983-9.
  6. Gonzalez L., Trigatti B.L. Macrophage apoptosis and necrotic core development in atherosclerosis: a rapidly advancing field with clinical relevance to imaging and therapy. Can J Cardiol 2017; 33(3): 303–312, https://doi.org/10.1016/j.cjca.2016.12.010.
  7. Werner N., Wassmann S., Ahlers P., Kosiol S., Nickenig G. Circulatin CD31+/annexin V+ apoptotic microparticles correlate with coronary endothelial function in patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2006; 26(1): 112–116, https://doi.org/10.1161/01.atv.0000191634.13057.15.
  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, https://doi.org/10.1007/s00380-018-1169-6.
  9. Garratt K.N., Edwards W.D., Kaufmann U.P., Vlietstra R.E., Holmes D.R. Jr. Differential histopathology of primary atherosclerotic and restenotic lesions in coronary arteries and saphenous vein bypass grafts: analysis of tissue obtained from 73 patients by directional atherectomy. J Am Coll Cardiol 1991; 17(2): 442–448, https://doi.org/10.1016/s0735-1097(10)80113-5.
  10. Kalinin R.E., Suchkov I.A., Klimentova E.A., Egorov A.A., Povarov V.O. Apoptosis in vascular pathology: present and future. Rossijskij mediko-biologiceskij vestnik imeni akademika I.P. Pavlova 2020; 28(1): 79–87.
  11. Singh R., Letai A., Sarosiek K. Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol 2019; 20(3): 175–193, https://doi.org/10.1038/s41580-018-0089-8.
  12. Clarke M.C., Figg N., Maguire J.J., Davenport A.P., Goddard M., Littlewood T.D., Bennett M.R. Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nat Med 2006; 12(9): 1075–1080, https://doi.org/10.1038/nm1459.
  13. Norata G.D., Tonti L., Roma P., Catapano A.L. Apoptosis and proliferation of endothelial cells in early atherosclerotic lesions: possible role of oxidised LDL. Nutr Metab Cardiovasc Dis 2002; 12(5): 297–305.
  14. Akishima Y., Akasaka Y., Ishikawa Y., Lijun Z., Kiguchi H., Ito K., Itabe H., Ishii T. Role of macrophage and smooth muscle cell apoptosis in association with oxidized low-density lipoprotein in the atherosclerotic development. Mod Pathol 2005; 18(3): 365–373, https://doi.org/10.1038/modpathol.3800249.
  15. Proudfoot D., Skepper J.N., Hegyi L., Bennett M.R., Shanahan C.M., Weissberg P.L. Apoptosis regulates human vascular calcification in vitro: evidence for initiation of vascular calcification by apoptotic bodies. Circ Res 2000; 87(11): 1055–1062, https://doi.org/10.1161/01.res.87.11.1055.
  16. Chen Y., Zhou H., He C., Wang T., Zhang G., Zhang P., Wang R., Wu Q., Yao Y. The oxLDL/β2GPI/anti-β2GPI antibody complex induces apoptosis of human umbilical vein endothelial cells by promoting the production of reactive oxygen species. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2019; 35(3): 223–229.
Klimentova E.A., Suchkov I.A., Shchulkin A.V., Glazkova A.P., Kalinin R.E. Expression of Apoptotic Markers Bcl-2 and Bax in the Vascular Wall. Sovremennye tehnologii v medicine 2021; 13(2): 46, https://doi.org/10.17691/stm2021.13.2.05


Journal in Databases

pubmed_logo.jpg

web_of_science.jpg

scopus.jpg

crossref.jpg

ebsco.jpg

embase.jpg

ulrich.jpg

cyberleninka.jpg

e-library.jpg

lan.jpg

ajd.jpg

SCImago Journal & Country Rank