Predictors of Coronary Atherosclerosis: HSP70, Markers of Oxidative Stress and Endothelial Dysfunction

ORIGINAL ARTICLE
Julia A. Kotova, Anna A. Zuikova, Aleksander N Pashkov, Natalia V. Strahova, Olga N. Krasnorutskaya

 
International Journal of Biomedicine. 2019;9(2):97-101.
DOI: 10.21103/Article9(2)_OA2
Originally published June 15, 2019  

Abstract: 

The aim of this study was to evaluate the role of HSP70, and markers of oxidative stress and endothelial dysfunction, as determinants of the severity of coronary atherosclerosis. The study revealed significant differences between groups with and without coronary atherosclerosis in terms of HSP70, superoxide dismutase (SOD), total homocysteine (tHcy) and markers of oxidative modification of proteins. Significant correlations between Gensini score, lipid profile parameters and studied markers were determined. The results of MLRA allow us to consider the levels of HSP70, tHcy, LDL-C and ketone derivative of 2.4-dinitrophenylhydrazine as factors associated with the risk of coronary atherosclerosis.

Keywords: 
coronary atherosclerosis • heat shock protein 70 • superoxide dismutase • oxidative modification of proteins • homocysteine
References: 
  1. Mendis S, Puska P, Norrving B, Organization WH, Federation WH, Organization WS. Global atlas on cardiovascular disease prevention and control. Geneva: World Health Organization; 2011. Available from: http://www.who.int/iris/handle/10665/44701
  2. WHO | Cardiovascular diseases (CVDs]. Geneva: World Health Organization; 2017. Available from: http://www.who.int/mediacentre/factsheets/fs317/en/
  3. Ragino YuI, Chernyavskij AM, Eremenko NV, Shakhtshnejder EV, Polonskaya YaV, Tsimbal SYu, Ivanova MV, Voevoda MI. [Key laboratory diagnostic biomarkers of coronary atherosclerosis]. Kardiologiia. 2011;51(3): 42-6. [Article in Russian].
  4. Vertkin AL, Topolyanskij AV. [The problem of hyperhomocysteinemia in cardiac patients]. Farmateka. 2007;15:10-14. [Article in Russian].
  5. L'vovskaya EI, Sahankova EN. [The ratio of levels of lipid peroxidation and oxidative modification of proteins in students 17-23 years (Kungur)]. Vestnik YUrGU. 2012; 21: 112-116. [Article in Russian].
  6. Musthafa QA, Abdul Shukor MF, Ismail NAS, Mohd Ghazi A, Mohd Ali R, M Nor IF, et al. Oxidative status and reduced glutathione levels in premature coronary artery disease and coronary artery disease. Free Radic Res. 2017 Oct;51(9-10):787-798. doi: 10.1080/10715762.2017.1379602.
  7. Zanozina OV, Brovkova NN, Shcherbatyuk TE. [Oxidized modified proteins in the atherosclerosis genesis at a diabetes mellitus of the 2nd type]. Sovremennye Tehnologii v Medicine. 2009; 2: 72-75. [Article in Russian].
  8. Bykova AA, Azizova OA, Dumikyan ASh, Shvachko AG, Sergienko VI, Syrkin AL. [Oxidative modification of fibrinogen in patients with coronary heart disease]. Rossijskij Kardiologicheskij Zhurnal. 2015;1:24. [Article in Russian].
  9. Fomina MA, Abalenihina YuV. Oxidative modification of tissue proteins with a change in the synthesis of nitric oxide. M: Gehotar-Media; 2018. [In Russian].
  10. Wick G, Knoflach M, Xu Q. Autoimmune and inflammatory mechanisms in atherosclerosis. Annu Rev Immunol. 2017; 22: 361-403.
  11. Trott A, West JD, Klaić L, Westerheide SD, Silverman RB, Morimoto RI, Morano KA. Activation of heat shock and antioxidant responses by the natural product celastrol: transcriptional signatures of a thiol-targeted molecule. Mol Biol Cell. 2008 Mar;19(3):1104-12. doi: 10.1091/mbc.E07-10-1004.
  12.  Wu CW, Biggar KK, Zhang J, Tessier SN, Pifferi F, Perret M, Storey KB. Induction of Antioxidant and Heat Shock Protein Responses During Torpor in the Gray Mouse Lemur, Microcebus murinus. Genomics Proteomics Bioinformatics. 2015 Apr;13(2):119-26. doi: 10.1016/j.gpb.2015.03.004.
  13. Juonala M, Viikari JS, Laitinen T, Marniemi J, Helenius H, Rönnemaa T, Raitakari OT. Interrelations between brachial endothelial function and carotid intima-media thickness in young adults: the cardiovascular risk in young Finns study. Circulation. 2004 Nov 2;110(18):2918-23.
  14. Davydchyk EV, Snezhitskiy VA, Nikonova LV. [Relationship of hyperhomocysteinemia with coronary heart disease and diabetes mellitus]. Journal of the Grodno State Medical University. 2015; (1):9-13.[Article in Russian].
  15. Guthikonda S, Haynes WG. Homocysteine: role and implications in atherosclerosis. Curr Atheroscler Rep. 2006 ;8(2):100-6.
  16. Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol. 1983 Feb;51(3):606.
  17. Dubinina EE, Burmistrov SO, Khodov DA, Porotov IG. [Oxidative modification of human serum proteins. A method of determining it].Vopr Med Khim. 1995;41(1):24-6. [Article in Russian].
  18. Vichova T1, Motovska Z. Oxidative stress: Predictive marker for coronary artery disease. Exp Clin Cardiol. 2013 Spring;18(2):e88-91.
  19. Huo Y, Wu X, Ding J, Geng Y, Qiao W, Ge A, et al. Vascular Remodeling, Oxidative Stress, and Disrupted PPARγ Expression in Rats of Long-Term Hyperhomocysteinemia with Metabolic Disturbance. PPAR Res. 2018 Jan 15;2018:6738703. doi: 10.1155/2018/6738703.
  20. Tyagi N, Qipshidze N, Sen U, Rodriguez W, Ovechkin A, Tyagi SC. Cystathionine beta synthase gene dose dependent vascular remodeling in murine model of hyperhomocysteinemia. Int J Physiol Pathophysiol Pharmacol. 2011 Sep 30;3(3):210-22.
  21. McCully KS. Homocysteine Metabolism, Atherosclerosis, and Diseases of Aging. Compr Physiol. 2015 Dec 15;6(1):471-505. doi: 10.1002/cphy.c150021.
  22. Giles WH, Croft JB, Greenlund KJ, Ford ES, Kittner SJ. Total homocyst(e)ine concentration and the likelihood of nonfatal stroke: results from the Third National Health and Nutrition Examination Survey, 1988-1994. Stroke. 1998 Dec;29(12):2473-7.
  23. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol. 1969 Jul;56(1):111-28.
  24. Kanwar YS, Manaligod JR, Wong PW. Morphologic studies in a patient with homocystinuria due to 5, 10-methylenetetrahydrofolate reductase deficiency. Pediatr Res. 1976 Jun;10(6):598-609.
  25. Bostom AG, Silbershatz H, Rosenberg IH, Selhub J, D'Agostino RB, Wolf PA, et al. Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med. 1999 May 24;159(10):1077-80.
  26. Ren J, Liu C, Zhao D, Fu J. The role of heat shock protein 70 in oxidant stress and inflammatory injury in quail spleen induced by cold stress. Environ Sci Pollut Res Int. 2018 Jul;25(21):21011-21023. doi: 10.1007/s11356-018-2142-8.
  27. Zhu J, Quyyumi AA, Wu H, Csako G, Rott D, Zalles-Ganley A, et al. Increased serum levels of heat shock protein 70 are associated with low risk of coronary artery disease. Arterioscler Thromb Vasc Biol. 2003 Jun 1;23(6):1055-9.
  28. Martin-Ventura JL, Leclercq A, Blanco-Colio LM, Egido J, Rossignol P, Meilhac O, Michel JB. Low plasma levels of HSP70 in patients with carotid atherosclerosis are associated with increased levels of proteolytic markers of neutrophil activation. Atherosclerosis. 2007 Oct;194(2):334-41.
  29. Wright BH, Corton JM, El-Nahas AM, Wood RF, Pockley AG. Elevated levels of circulating heat shock protein 70 (Hsp70) in peripheral and renal vascular disease. Heart Vessels. 2000;15(1):18-22.
  30. Xie F, Zhan R, Yan LC, Gong JB, Zhao Y, Ma J, Qian LJ. Diet-induced elevation of circulating HSP70 may trigger cell adhesion and promote the development of atherosclerosis in rats. Cell Stress Chaperones. 2016 Sep;21(5):907-14. doi: 10.1007/s12192-016-0716-2.
  31. Rodríguez-Iturbe B, Johnson RJ. Heat shock proteins and cardiovascular disease. Physiol Int. 2018 Mar 1;105(1):19-37. doi: 10.1556/2060.105.2018.1.4.
  32. Bielecka-Dabrowa A, Barylski M, Mikhailidis DP, Rysz J, Banach M. HSP 70 and atherosclerosis--protector or activator? Expert Opin Ther Targets. 2009 Mar;13(3):307-17. doi: 10.1517/14728220902725149.
  33. Pockley AG, Georgiades A, Thulin T, de Faire U, Frostegård J.  Serum heat shock protein 70 levels predict the development of atherosclerosis in subjects with established hypertension. Hypertension. 2003 Sep;42(3):235-8.
  34. Dulin E, García-Barreno P, Guisasola MC. Extracellular heat shock protein 70 (HSPA1A) and classical vascular risk factors in a general population. Cell Stress Chaperones. 2010 Nov;15(6):929-37. doi: 10.1007/s12192-010-0201-2.
  35. Marber MS, Mestril R, Chi SH, Sayen MR, Yellon DM, Dillmann WH. Overexpression of the rat inducible 70-kD heat stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury. J Clin Invest. 1995 Apr;95(4):1446-56.
  36. Plumier JC, Ross BM, Currie RW, Angelidis CE, Kazlaris H, Kollias G, Pagoulatos GN. Transgenic mice expressing the human heat shock protein 70 have improved post-ischemic myocardial recovery. J Clin Invest. 1995 Apr;95(4):1854-60.
  37. Radford NB, Fina M, Benjamin IJ, Moreadith RW, Graves KH, Zhao P, et al. Cardioprotective effects of 70-kDa heat shock protein in transgenic mice. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2339-42.
  38. Trost SU, Omens JH, Karlon WJ, Meyer M, Mestril R, Covell JW, Dillmann WH. Protection against myocardial dysfunction after a brief ischemic period in transgenic mice expressing inducible heat shock protein 70. J Clin Invest. 1998 Feb 15;101(4):855-62.

Download Article
Received May 14, 2019.
Accepted June 12, 2019.
©2019 International Medical Research and Development Corporation.