The Influence of Therapy for Secondary Prevention of Coronary Heart Disease on Fatty ACID Content of Blood Serum, Liver T and Myocardium of Rats under Hyperholesterol Diet

DOI: 10.22138/2500-0918-2018-15-1-71-86

M.Yu. Kotlovsky, A.M. Dygai, O.Yu. Trifonova, V.V. Zhdanov, V.V. Udut, A.A. Churin, I.Yu. Yakimovich, V.N. Titov, E.V. Krasnov, L.Yu. Kotlovskya

Goldberg Research Institute of Pharmacology and Regenerative Medicine, Тomsk, Russian Federation;
Siberian State Medical University, Тomsk, Russian Federation;
National medical research center of cardiology of the Ministry of healthcare of the Russian Federation, Moscow, Russian Federation

Аabstract. Objective. To examine the impact of the minimum therapeutic dose of the statin and the mechanisms of the induced changes in the quantitative and qualitative characteristics of lipoprotein (LP), fatty acids (FA), cholesterol of blood serum, liver and myocardium in secondary prevention of coronary heart disease (CHD). Methods. Male rats (Wistar) got cholesterol, simvastatin (0.1 mg/day) and other drugs. PL of blood serum was determined by the analyzer COBAS INTEGRA 400 plus (USA). The contents of the FA and cholesterol were investigated by chromatography-mass-spectrometer (Аgilent Technologies, USA). Results. Simvastatin redistributed FA and cholesterol in blood serum and tissues, by hepatocytes absorption in composition of LP. The value of FA (blood serum, myocardium) has been changed mainly due to unsaturated fatty acids (UFA). The absorption of polyunsaturated (PUFA), monounsaturated (MUFAS) and saturated (SFA) FA, prevailed over their endogenous formation. The formation of PUFA, SFA-increased, and MUFA has dropped. The synthesis of MUFA was inferior to that of SFA, which reduced the neutralization of the pathological action of palmitic (C16:0) SFA. The ratio ω3/ω6 PUFA in the blood serum changed in the direction of the ω6 PUFA, and C20:5/C20:4 in the direction of arachidonic (C20:4) UFA. The decrease UFA in blood serum and myocardium occurred, mostly due to the MUFA, resulting in a decreased antioxidant protection. There was a decrease in the absolute content of energy substrates in the blood serum and the myocardium of rats and changes in their qualitative composition. In cardiomyocytes the ratio of the formation/oxidation of C18:1(9) ω9 MUFA has been shifted in the direction of β-oxidation. The statin and the combination of bisoprolol and acetylsalicylic acid had the opposite direction of the effects on the value of the indicators, with a stronger influence of the last. At the same time the effect of the drug is ω3 UFA are one-directional influence of statin (liver and myocardium), but weaker. Conclusion. Simvastatin, minimal dose, with a positive main effect, demonstrated a negative effect upon the metabolism of fatty acids that were eliminated in conjunction with statin taking bisoprolol and acetylsalicylic acid.

Keywords: fatty acids, ischemic heart disease, simvastatin

Received 27.12.2017

For citation:
M.Yu. Kotlovsky, A.M. Dygai, O.Yu. Trifonova, V.V. Zhdanov, V.V. Udut, A.A. Churin, I.Yu. Yakimovich, V.N. Titov, E.V. Krasnov, L.Yu. Kotlovskya. The Influence of Therapy for Secondary Prevention of Coronary Heart Disease on Fatty ACID Content of Blood Serum, Liver T and Myocardium of Rats under Hyperholesterol Diet. Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2018, Vol. 15, no. 1, pp. 71–86. DOI: 10.22138/2500-0918-2018-15-1-71-86 (In Russ)

REFERENCES
1. Cheung B.M., Lauder I.J., Lau C.P. et al. Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes. Br. J. Clin. Pharmacol. – 2004. – Vol. 57. No. 5. pp. 640-651.
2. Martsevich S. Yu., Gaisionok O. V., Tripkosh S.G. Real Practice of Statins Use and its Dependence on Follow-up in the Specialized Medical Centre in Patients with High Cardiovascular Risk (According to the PROFILE Register). Rational Pharmacotherapy in Cardiology. 2013. No. 9(4). pp. 362-367 (In Russ)
3. Titov V.N., Lisitsin D.M. Fat acids. Physical chemistry, biology and medicine – M.-Tver: Triada, 2006. 672 p. (In Russ)
4. Poldermans D., Boersma E., Bax J. et al. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. N. Engl. J. Med. 1999. Vol. 341. pp. 1789-1794.
5. Shilov A.M., Sviatov I.S., Sanodze I.D. Antirepressants – the Current State of the Question. Russian Medical Journal. 2003. No. 11(9). pp. 552-556 (In Russ).
6. Marchioli R., Barzi F., Bomba E. et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’ Infarto Miocardico (GISSI)-Prevenzione. Circulation. 2002. Vol. 105. No. 16. pp. 1897-1903.
7. Utzschneider К.M., Kahn S.E. The Role of Insulin Resistance in Nonalcoholic Fatty Liver Disease. Clin. Endocrinol. Metab. 2006. Vol. 91. No. 12. pp. 4753-4761.
8. Nielsen L.B., Bartels E.D., Bollano E. Overexpression of apolipoprotein B in the heart impedes cardiac triglyceride accumulation and development of cardiac dysfunction in diabetic mice. J. Biol. Chem. 2002. Vol. 277. pp. 27014-27020.
9. Reaven P.D., Grass B.J., Tribble D.L. Effects of linoleate-enriched and oleate-enriched diets in combination with α-tocopherol on the susceptibility of low-density lipoproteins (LDL) and LDL subfractions to oxidative modification in humans. Arterioscler. Thromb. 1994. Vol. 14. pp. 557-566.
10. Houmard J.A., Tanner C.J., Yu C. Effect of weight loss on insulin sensitivity and intramuscular long-chain fatty Acyl-CoAs in morbidly obese subjects. Diabetes. 2002. Vol. 51. pp. 2959-2963.
11. Watt M.J., Spriet L.L. Triacylglycerol lipases and metabolic control: implications for health and disease. Am. J. Physiol. Metab. 2010. Vol. 299. pp. 162–168.
12. Pchelintsev M.V. Clinical and pharmacological effects of eicosapentanoic and docosahexaenoic (omega-3) acids in the treatment of coronary heart disease and the prevention of sudden cardiac death with evidence-based medicine. Cardiology. 2010. V. 50. No.3. pp. 74-82. (In Russ).
13. Gillingham L.G., Gustafson J.A., Han S.Y. et al. High-oleic rapeseed (canola) and flaxseed oils modulate serum lipids and inflammatory biomarkers in hyper cholesterolaemic subjects. Br. J. Nutr. 2011. Vol. 105. No. 3. pp. 417-427.
14. Harper C.R., Jacobson T.A. The fats of life. Arch. Intern. Med. 2001. Vol. 161. pp. 2185-2192.
15. Delarue J., Magnan C. Free fatty acids and insulin resistance. Curr. Opin. Clin. Nutr. Metab. Care. 2007. Vol. 10. No. 2. pp. 142-148.
16. Mensink R.P. Effects of stearic acid on plasma lipid and lipoproteins in humans. Lipids. 2005. Vol. 40. pp. 1201-1205. 
17. Jiang Z., Michal J., Wu X.L. et al. The Heparan and Heparin Metabolism Pathway is Involved in Regulation of Fatty Acid Composition J. Int. J. Biol. Sci. 2011. Vol. 7. No. 5. pp. 659-663.
18. Listenberger L.L., Ory D.S., Schaffer J. Palmitate-induced apoptosis can occur through a ceramide-independent pathway. J. Biol. Chem. 2001. Vol. 276. pp. 14890-14895.
19. MacDonald J.I.S., Sprecher H. Phospholipid fatty acid remodeling in mammalian cells. Biochim. Biophys. Аcta. 1991. Vol. 1084. pp. 105-119.

Authors
Mikhail Yu.Kotlovsky 
Goldberg Research Institute of Pharmacology and Regenerative Medicine of Tomsk National Research Medical Center
Cand. Sci. (Med.), Research Fellow 
Russian Federation, 634028, Tomsk, Lenin Prospect, 3 
m.u.kotlovskiy11443@mail.ru

Aleksandr M. Digai 
Goldberg Research Institute of Pharmacology and Regenerative Medicine of Tomsk National Research Medical Center
Honored Worker of Science of the Russian Federation, Academician of the Russian Academy of Sciences, Dr. Sci.(Med.), Professor, Secretary of the Life Science Section of the Russian Academy of Science Medical Department, Academic Advisor of Goldberg Research Institute of Pharmacology and Regenerative Medicine of Tomsk National Research Medical Center
Russian Federation, 634028, Tomsk, Lenin Prospect, 3 
nii@pharmso.ru

Olga Yu. Trifonova 
Goldberg Research Institute of Pharmacology and Regenerative Medicine of Tomsk National Research Medical Center
Dr. Sci. (Med.), Cardiologist of the Department of Therapy 
Russian Federation, 634028, Tomsk, Lenin Prospect, 3 
trifonova61@mail.ru

Vadim V. Zhdanov 
Goldberg Research Institute of Pharmacology and Regenerative Medicine of Tomsk National Research Medical Center
Dr. Sci. (Med.), Professor, Principal of of the Goldberg Research Institute of Pharmacology and Regenerative Medicine of Tomsk National Research Medical Center
Russian Federation, 634028, Tomsk, Lenin Prospect, 3 
zhdanov_vv@pharmso.ru

Vladimir V. Udut 
Goldberg Research Institute of Pharmacology and Regenerative Medicine of Tomsk National Research Medical Center
Honored Worker of Science of the Russian Federation, Corresponding Member of the Russian Academy of Science, Dr. Sci. (Med.), Professor, Deputy Director for Scientific and Medical Works of the Goldberg Research Institute of Pharmacology and Regenerative Medicine of Tomsk National Research Medical Center, Head of the Physiology, Molecular and Clinical Pharmacology Laboratory
Russian Federation, 634028, Tomsk, Lenin Prospect, 3 
udutv@mail.ru

Aleksei A. Churin 
Goldberg Research Institute of Pharmacology and Regenerative Medicine of Tomsk National Research Medical Center
Dr. Sci. (Med.), Deputy Director for Preclinical Research Standartization of the Goldberg Research Institute of Pharmacology and Regenerative Medicine of Tomsk National Research Medical Center, Head of the Medical Toxicology Department
Russian Federation, 634028, Tomsk, Lenin Prospect, 3 
churin_aa@pharmso.ru

Inessa Yu. Yakimovich 
Siberian State Medical University
Cand. Sci. (Med.), Associate Professor, Head of the Department of Hygiene 
Russian Federation, 634050, Tomsk, Moscow tract, 2
iness2501@yandex.ru

Vladimir N. Titov 
Myasnikov Institute of Cardiology 
Dr. Sci. (Med.), Professor, Head of the Clinical Biochemistry Laboratory 
Russian Federation, 121552, Moscow, Cherepkovskaya street, 15a
vn_titov@mail.ru

Evgeny V. Krasnov 
Siberian State Medical University
Assistant Professor of the Department of Hygiene
Russian Federation, 634028, Tomsk, Lenin Prospect, 3
evkrasnov@gmail.com

Larisa Yu. Kotlovskaya 
Siberian State Medical University
Assistant Professor of the Department of Hygiene
Russian Federation, 634028, Tomsk, Lenin Prospect, 3
lars.ktl@gmail.com

 
 
 

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