This journal is
indexed in Scopus
Year 2018 Vol. 26 No 2
GENERAL & SPECIAL SURGERY
V.A. LAZARENKO, E.A. BOBROVSKAYA
HYPERHOMOCYSTEINEMIA AND FUNCTIONAL STATE OF ENDOTHELIUM IN PATIENTS WITH PERIPHERAL ARTERY DISEASE WITH ARTERIAL RECONSTRUCTIONS
Kursk State Medical University, Kursk,
The Russian Federation
Objective. To study the relationship between homocysteine and markers of the functional state of the endothelium in patients with obliterating atherosclerosis in operations on the aorta and arteries of the lower limbs.
Methods. The study included 68 patients with peripheral artery disease, the average age was 57.8±7.3 years, with II B – III degree of chronic arterial insufficiency according to R. Fontaine-A.V. Pokrovsky, who were divided into three groups: I group underwent the femoro-popliteal bypass (n=32), II – the aorto-femoral bypass (n=20), III – x-ray endovascular angioplasty and stenting of the iliac arteries (n=16). A correlation analysis was made between the content of homocysteine and the markers of the endothelium functional state of: the oxidized low-density lipoproteins (oxidized LDL), a molecule of adhesion of the vascular endothelium type 1 (sVCAM-1), the tissue type 1 plasminogen activator inhibitor (PAI-1), the tissue plasminogen activator (t-PA), Annexin V in the systemic and local bloodstream prior to surgery and after the arterial reconstructions.
Results. Correlation relationships between homocysteine and oxidized LDL were established both in the systemic blood flow and the affected limb, this association persisted after the reconstructive intervention, the most significant in the local bloodstream after femoro-popliteal bypass surgery. Preoperative positive correlation of the systemic level of homocysteine and sVCAM-1 in group I was marked. The effect of homocysteine on the fibrinolytic function of the endothelium was shown, as indicated by the direct correlation between homocysteine and PAI-1 in the systemic blood flow and in the affected limb, which persist after open reconstructions. Significant links between homocysteine and the level of Annexin V were revealed in the group of patients with the lesion of the femoro-popliteal arterial segment.
Conclusions. Hyperhomocysteinemia contributes significantly to the disturbance of the endothelium functional state, affecting apoptosis, the activation of atherogenic LDL, and the procoagulant potential, which persist even after arterial reconstructions both in the systemic and local bloodstream.
- Petrishchev NN, Vasina LV, Vlasov TD, Gavrisheva NA, Menshutina MA. Tipovye formy disfunktsii endoteliia. Klin-Lab Konsilium. 2007;(18):31-35. (in Russ.)
2.Tsybikova NM, Tsybikov MN. Rol’ gipergomotsisteinemii v patologii cheloveka. Dal’nevostoch Med Zhurn. 2007;(4):110-112. (in Russ.)
- Chia S, Wilson R, Ludlam CA, Webb DJ, Flapan AD, Newby DE. Endothelial dysfunction in patients with recent myocardial infarction and hyperhomocysteinaemia: effects of vitamin supplementation. ClinSci (Lond). 2005 Jan;108(1):65-72. doi: 10.1042/CS20040150.
- Steed MM, Tyagi SC. Mechanisms of cardiovascular remodeling in hyperhomocysteinemia. Antioxid Redox Signal. 2011 Oct 1;15(7):1927-43. doi: 10.1089/ars.2010.3721.
- Loscalzo J. Homocysteine-mediated thrombosis and angiostasis in vascular pathobiology. J Clin Invest. 2009 Nov;119(11):3203-5. doi: 10.1172/JCI40924.
- Lazarenko VA, Bobrovskaya EA, Sorokin A.V. Hyperhomocysteinemia: peripheral atherosclerosis and
reconstructive surgery. Kursk Nauch-Prakt Vestn «Chelovek i Ego Zdorov’e». 2014;(4):63-66. (in Russ.)
- Zobova DA, Kozlov SA. Rol’ gomotsisteina v patogeneze nekotorykh zabolevanii. Izv Vysshikh Ucheb Zavedenii. Povolzh Region. Med Nauki. 2016;3(39):132-44. doi: 10.21685/2072-3032-2016-3-15. (in Russ.)
- Loscalzo J. The oxidant stress of hyperhomocyst(e)inemia. J Clin Invest. 1996 Jul 1;98(1):5-7. doi: 10.1172/JCI118776.
- Ingenbleek Y. The Oxidative stress of hyperhomocysteinemia results from reduced bioavailability of sulfur-containing reductants. Open Clin Chem J. 2011;4(1):34-44. doi: 10.2174/1874241601104010034.
- Karazhanova LK, Zhunuspekova AS. Hyperhomocysteinemia as a risk factor of cardiovascular diseases (literature review). Nauka i Zdravookhranenie. 2016;(4):129-44. orcid.org/0000-0003-1496-3281. (in Russ.)
- Leoncini G, Bruzzese D, Signorello MG. Activation of p38 MAPKinase/cPLA2 pathway in homocysteine-treated platelets. J Thromb Haemost. 2006;4(1):209-16. doi: 10.1111/j.1538-7836.2005.01708.x.
- Yeh JK, Chen CC, Hsieh MJ, Tsai ML, Yang CH, Chen DY, Chang SH, Wang CY, Lee CH, Hsieh IC. Impact of homocysteine level on long-term cardiovascular outcomes in patients after coronary artery stenting. J Atheroscler Thromb. 2017 Jul 1;24(7):696-705. doi: 10.5551/jat.36434.
- Tofler GH, Massaro J, O’Donnell CJ, Wilson PWF, Vasan RS, Sutherland PA, Meigs JB, Levy D, D’Agostino RB Sr. Plasminogen activator inhibitor and the risk of cardiovascular disease: The framingham heart study. Thromb Res. 2016 Apr;140:30-35. doi: 10.1016/j.thromres.2016.02.002.
- de Jong SC, Stehouwer CD, van-den Berg M, Vischer UM, Rauwerda JA, Emeis JJ. Endothelial marker proteins in hyperhomocysteinemia. ThrombHaemost. 1997 Nov;78(5):1332-37.
- Sipkens JA, Hahn N, van den Brand CS, Meischl C, Cillessen SA, Smith DE, Juffermans LJ, Musters RJ, Roos D, Jakobs C, Blom HJ, Smulders YM, Krijnen PA, Stehouwer CD, Rauwerda JA, van Hinsbergh VW, Niessen HW. Homocysteine-induced apoptosis in endothelial cells coincides with nuclear NOX2 and peri-nuclear NOX4 activity. Cell Biochem Biophys. 2013 Nov;67(2):341-52. doi: 10.1007/s12013-011-9297-y.
305041, The Russian Federation,
Kursk, K.Marx Str., 3,
Kursk State Medical University,
Department of Surgical Diseases
of the Faculty of Post-Graduate Training,
Tel.: +7 (4712) 58-81-32,
Lazarenko Viktor A.
Lazarenko Viktor A., MD, Professor, Rector, Head of the Department of Surgical Diseases of the Faculty of Post-Graduate Training, Kursk State Medical University, Kursk, Russian Federation.
Bobrovskaya Elena A., PhD, Associate Professor of the Department of Surgical Diseases of the Faculty of Post-Graduate Training, Kursk State Medical University, Kursk, Russian Federation.