UDC

616.12-008.331-092

Authors

Sergey G. Krivoshchekov
Scientific Research Institute of Physiology and Basic Medicine
4 Akademika Timakova St., Novosibirsk, 630117, Russian Federation;
e-mail: krivosch@physiol.ru
Irina Y. Suvorova
Scientific Research Institute of Physiology and Basic Medicine
4 Akademika Timakova St., Novosibirsk, 630117, Russian Federation;
e-mail: suvorovaiu@physiol.ru
Vladimir N. Maksimov
Scientific Research Institute of Therapy and Preventive Medicine
175/1 Borisa Bogatkova St., Novosibirsk, 630089, Russian Federation;
e-mail: medik11@mail.ru
Viktor I. Baranov
Scientific Research Institute of Physiology and Basic Medicine
4 Akademika Timakova St., Novosibirsk, 630117, Russian Federation;
e-mail: v.i.baranov@physiol.ru
Igor V. Shevchenko
Scientific Research Institute of Physiology and Basic Medicine
4 Akademika Timakova St., Novosibirsk, 630117, Russian Federation;
e-mail: ShevchenkoIV@physiol.ru
Vladimir N. Melnikov
Scientific Research Institute of Physiology and Basic Medicine
4 Akademika Timakova St., Novosibirsk, 630117, Russian Federation;
e-mail: mevlanic@yandex.ru
Kseniya N. Kolesnik
Scientific Research Institute of Therapy and Preventive Medicine
175/1 Borisa Bogatkova St., Novosibirsk, 630089, Russian Federation;
e-mail: ksenya-kolesnik@mail.ru
Anastasiya A. Ivanova
Scientific Research Institute of Therapy and Preventive Medicine
175/1 Borisa Bogatkova St., Novosibirsk, 630089, Russian Federation;
e-mail: ivanova_a_a@mail.ru

Abstract

One of the significant complications of hypertension is left ventricle hypertrophy. However, it is diagnosed only in half of the hypertensive patients. It is believed that the shape of the heart usually changes due to cardiomyocyte hypertrophy as well as hypertrophy and hyperplasia of interstitial and endothelial cells, which eventually results in increased heart size and volume. The research aimed to find candidate genes affecting myocardial remodelling as well as to study the connection between candidate gene polymorphism and the type of myocardial remodelling in 84 hypertensive patients using both clinical, physiological and biochemical methods. Each patient underwent echocardiography to determine the geometric model of the left ventricle according to A. Ganau’s classification. The following candidate genes were tested for polymorphism: 1) gene coding the components of the renin–angiotensin system (ACE), 2) gene of key sympathetic receptors (ADRA2B), 3) gene whose defects can result in endothelial dysfunction (NOS3). The control group consisted of normotensive subjects examined in the course of WHO-based international projects. The results showed statistically significant differences in prevalence of ACE-II and -ID genotypes between the patients and controls. The patients with homozygous insertion allelotypes of ACE и ADRA2B genes were more predisposed to concentric hypertrophy. No statistically significant differences were found for NOS3 gene polymorphisms. However, a link between these polymorphisms and the process of remodelling was observed.

Keywords

hypertension, myocardial remodelling, genetic polymorphism, АСЕ gene, NOS3 gene, ADRA2B gene, remodelling predictors

References

1. Kobalava Zh.D., Kotovskaya Yu.V. Arterial’naya gipertoniya 2000: klyuchevye aspekty diagnostiki, differentsial’noy diagnostiki, profilaktiki, kliniki, lecheniya [Hypertension 2000: The Key Aspects of Diagnosis, Differential Diagnosis, Prevention, Clinical Picture, and Treatment]. Moscow, 2001.
   
2. Swynghedauw B. Molecular Mechanisms of Myocardial Remodeling. Physiol. Rev., 1999, vol. 79, no. 1, pp. 215–262.
   
3. Ryazanov A.S. Kliniko-geneticheskie aspekty razvitiya gipertrofii miokarda levogo zheludochka [Clinical and Genetic Aspects of the Development of Left Ventricular Hypertrophy]. Rossiyskiy kardiologicheskiy zhurnal, 2003, no. 2, pp. 93–98.
   
4. Menick D.R., Li M.S., Chernysh O., Renaud L., Kimbrough D., Kasiganesan H., Mani S.K. Transcriptional Pathways and Potential Therapeutic Targets in the Regulation of Ncx Expression in Cardiac Hypertrophy and Failure. Adv. Exp. Med. Biol., 2013, no. 961, pp. 125–135.
   
5. Krivoshchekov S.G., Pinigina I.A. Strukturno-funktsional’nye osobennosti serdechno-sosudistoy sistemy i metabolicheskikh pokazateley u molodykh zhiteley Yakutii s normal’nym i povyshennym urovnem arterial’nogo davleniya [Structural and Functional Features of the Cardiovascular System and Metabolic Indicators in Young Inhabitants of Yakutia with Normal and High Arterial Pressure]. Byulleten’ SO RAMN, 2009, no. 6, pp. 100–108.
   
6. Pinigina I.A., Makharova N.V., Krivoschekov S.G. Structural-Functional Changes in the Cardiovascular System During High Athletic Activity in Aboriginals of Yakutia. Human Physiology, 2010, vol. 36, no. 2, pp. 238–244.
   
7. Krivoschekov S.G., Pinigina I.A. Cardiovascular Adaptation to High Physical Activity in the North. Int. J. Circumpolar Health, 2010, no. 7, pp. 174–178.
   
8. Poteshkina N.G., Dzhanashiya P.Kh. Strukturno-funktsional’noe remodelirovanie miokarda i prognozirovanie aritmiy u bol’nykh arterial’noy gipertoniey [Myocardial Structural and Functional Remodeling and Prediction of Arrhythmias in Patients with Arterial Hypertension]. Arterial’naya gipertenziya, 2005, no. 4, pp. 249–251.
   
9. Khurs E. Remodelirovanie serdtsa pri arterial’noy gipertenzii [Cardiac Remodelling in Hypertension]. Lambert Academic Publishing, 2013.
   
10. Linde E.V., Akhmetov I.I., Ordzhonikidze Z.G. Vliyanie polimorfizmov genov ase , ppara , ppard i nfatc 4 na kliniko-funktsional’nye kharakteristiki “sportivnogo serdtsa” [The Effect of Polymorphisms in the ACE, PPARA, PPARD, and NFATC4 Genes on the Clinical and Functional Characteristics of “Athlete’s Heart”]. Mezhdunarodnyy zhurnal interventsionnoy kardioangiologii, 2009, no. 17, pp. 50–56.
    
11. Akhmetov I.I., Linde E.V., Rogozkin V.A. Assotsiatsiya polimorfizmov genov-regulyatorov s tipom adaptatsii serdechno-sosudistoy sistemy k fizicheskim nagruzkam [Association of Polymorphisms in Regulator Genes with the Type of Adaptation of the Cardiovascular System to Physical Loads]. Vestnik sportivnoy nauki, 2008, no. 1, pp. 38–41.
    
12. Linde E.V., Akhmetov I.I., Ordzhonikidze Z.G. Geneticheskie faktory i formirovanie gipertrofii miokarda levogo zheludochka u vysokokvalifitsirovannykh sportsmenov [Genetic Factors and Formation of Left Ventricular Hypertrophy in Elite Athletes]. Nauka i sport: Sovremennye tendentsii, 2014, no. 2(3), pp. 32–42.
    
13. Poteshkina N.G., Dzhanashiya P.Kh., Selivanova G.B. Arterial’naya gipertenziya [Hypertension]. Moscow, 2007.
    
14. Brugada R., Kelsey W., Lechin M., Zhao G., Yu Q.T., Zoghbi W., Quinones M., Elstein E., Omran A., Rakowski H., Wigle D., Liew C.C., Sole M., Roberts R., Marian A.J. Role of Candidate Modifier Genes on the Phenotypic Expression of Hypertrophy in Patients with Hypertrophic Cardiomyopathy. J. Investig. Med., 1997, no. 45(9), pp. 542–551.
    
15. Stepanov V.A., Puzyrev K.V. Polimorfizm genov angiotenzinprevrashchayushchego fermenta i endotelial’noy sintazy okisi azota u lits s arterial’noy gipertenziey, gipertrofiey miokarda levogo zheludochka i gipertroficheskoy kardiomiopatiey [Polymorphism of Angiotensin Converting Enzyme and Endothelial Nitric Oxide Synthase Genes in Patients with Hypertension, Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy]. Genetika, 1998, no. 34, pp. 1578–1581.
    
16. Karpov R.S., Puzyrev K.V. Molekulyarno-geneticheskiy analiz gipertrofii miokarda levogo zheludochka [Molecular-Genetic Analysis of Left Ventricular Hypertrophy]. Kardiologiya, 2001, no. 6, pp. 25–30.
    
17. Paukov V.S., Litvitskiy P.F. Patologiya [Pathology]. Moscow, 2004.
    
18. Mal’tseva L.D., Balalykin D.A., Litvitskiy P.F. Predstavleniya erasistrata o sisteme krovoobrashcheniya i ee roli v patologii [Erasistratus’s View on Blood Circulation System and Its Role in Pathology]. Kurskiy nauchno-prakticheskiy vestnik “Chelovek i ego zdorov’e”, 2015, no. 2, pp. 103–108.
    
19. Shlyakhto E.V., Konradi A.O., Zvartau N.E. Arterial’naya gipertenziya [Hypertension]. Kardiologiya: natsional’noe rukovodstvo [Cardiology: National Guidelines]. 2nd ed. Moscow, 2015.
    
20. Kuz’mina S.V., Mutaf’yan O.A., Larionova V.I. Polimorfizm genov renin-angiotenzin-al’dosteronovoy sistemy u detey i podrostkov s arterial’noy gipertenziey [Renin-Angiotensin-Aldosterone System Gene Polymorphism and Arterial Hypertension in Children]. Arterial’naya gipertenziya, 2009, no. 4, pp. 475–480.
    
21. Kuz’mina S.V. Osobennosti remodelirovaniya miokarda levogo zheludochka v zavisimosti ot geneticheskikh faktorov u detey s arterial’noy gipertenziey: avtoref. dis. … kand. med. nauk [Left Ventricle Remodelling Depending on Genetic Factors in Children with Hypertension: Cand. Med. Sci. Diss. Abs.]. St. Petersburg, 2010.
    
22. Eliseeva M.R., Khamidullaeva G.A., Srozhidinova N.Z., Abdullaeva G.Zh., Kurbanova D.R., Karimova B.Sh., Kevorkov A.G., Nagay A.V., Abdullaev A.A. Molekulyarno-geneticheskie aspekty essentsial’noy gipertenzii [Molecular- Genetic Aspects of Essential Hypertension]. Tashkent, 2009.
    
23. Khamidullaeva G.A., Eliseeva M.R., Srozhidinova N.Z., Abdullaeva G.Zh. Osobennosti raspredeleniya polimorfnykh markerov genov renin-angiotenzin-al’dosteronovoy sistemy, svyaz’ s gipertrofiey levogo zheludochka u bol’nykh essentsial’noy gipertoniey uzbekskoy natsional’nosti [Distribution of Polymorphic Markers of the Renin- Angiotensin-Aldosterone System Genes, and the Connection to Left Ventricular Hypertrophy in Uzbek Patients with Essential Hypertension]. Kardiologiya, 2007, vol. 47, no. 4, pp. 54–58.
    
24. Kuznetsova T.Yu., Gavrilov D.V., Dudanov I.P., Makarevich P.I., Balatskiy A.V., Samokhodskaya L.M., Parfenova E.V. Vliyanie polimorfizmov endotelial’noy NO sintazy i NADPH-oksidazy na razvitie oslozhneniy arterial’noy gipertenzii [The Influence of Polymorphisms of Endothelial Nitric Oxide Synthase and NADPH Oxidase Genes on the Development of Complications of Arterial Hypertension]. Kardiologiya, 2008, no. 3, pp. 27–33.
    
25. Malik F.S., Lavie C.J., Mehra M.R., Milani R.V., Re R.N. Renin-Angiotensin System: Genes to Bedside. Am. Heart J., 1997, vol. 134, no. 3, pp. 514–527.
    
26. Schelling P., Fischer H., Ganten D. Angiotensin and Cell Growth: A Link to Cardiovascular Hypertrophy? J. Hypertens., 1991, vol. 9, no. 1, pp. 3–15.
    
27. Lechin M., Quiñones M.A., Omran A., Hill R., Yu Q.-T., Rakowski H., Wigle D., Liew C.C., Sole M., Roberts R., Marian A.J. Angiotensin-I Converting Enzyme Genotypes and Left Ventricular Hypertrophy in Patients with Hypertrophic Cardiomyopathy. Circulation, 1995, no. 92, pp. 1808–1812.
    
28. Pfeufer A., Osterziel K.J., Urata H., Borck G., Schuster H., Wienker T.F., Dietz R., Luft F.C. Angiotensin- Converting Enzyme and Heart Chymase Gene Polymorphisms in Hypertrophic Cardiomyopathy. Am. J. Cardiol., 1996. vol. 78, no. 3, pp. 362–364.
    
29. Khromova A.V., Feliksova O.M., Kuba A.A., Bebyakova N.A. Analiz vliyaniya strukturnoy perestroyki promotora gena NOS3 na produktsiyu vazoaktivnykh endotelial’nykh faktorov [The Effect of Structural Adjustment in NOS3 Gene Promoter on the Production of Endothelium-Derived Vasoactive Factors]. Vestnik Severnogo (Arkticheskogo) federal’nogo universiteta. Ser.: Mediko-biologicheskie nauki, 2015, no. 4, pp. 107–115.
    
30. Minushkina L.O., Zateyshchikov D.A., Zateyshchikova A.A., Chistyakov D.A., Nosikov V.V., Sidorenko B.A. Polimorfizm gena endotelial’noy NO-sintazy i gipertrofii miokarda u bol’nykh arterial’noy gipertenziey [Polymorphism of Endothelial NO-Synthase and Myocardial Hypertrophy Genes in Patients with Arterial Hypertension]. Kardiologiya, 2002, no. 3, pp. 30–34.
    
31. Snapir A., Mikkelsson J., Perola M., Penttilä A., Scheinin M., Karhunen P.J. Variation in the Alpha2BAdrenoceptor Gene as a Risk Factor for Prehospital Fatal Myocardial Infarction and Sudden Cardiac Death. J. Am. Coll. Cardiol., 2003, vol. 41, no. 2, pp. 190–194.
    
32. Gaunau A., Devereux R.B., Roman M.J., de Simone G., Pickering T.G., Saba P.S., Vargiu P., Simongini I., Laragh J.H. Patterns of Left Ventricular Hypertrophy and Geometric Remodeling in Essential Hypertension. J. Am. Coll. Cardiol., 1992, vol. 19, no. 7, pp. 1550–1558.
    
33. Wang X.L., Sim A.S., Badenhop R.F., McCredie R.M., Wilcken D.E. A Smoking-Dependent Risk of Coronary Artery Disease Associated with a Polymorphism of the Endothelial Nitric Oxide Synthase Gene. Nat. Med., 1996, vol. 2, no. 1, pp. 41–45.
    
34. Lindpaintner K., Pfeffer M.A., Kreutz R., Stampfer M.J., Grodstein F., LaMotte F., Buring J., Hennekens C.H. A Prospective Evaluation of an Angiotensin-Converting-Enzyme Gene Polymorphism and the Risk of Ischemic Heart Disease. N. Engl. J. Med., 1995, vol. 332, no. 11, pp. 706–712.
    
35. Heesen W.F., Beltman F.W., May J.F., Smit A.J., de Graeff P.A., Havinga T.K., Schuurman F.H., van der Veur E., Hamer J.P., Meyboom-de Jong B., Lie K.I. High Prevalence of Concentric Remodeling in Elderly Individuals with Isolated Systolic Hypertension from a Population Survey. Hypertension, 1997, vol. 29, no. 2, pp. 539–543.
    
36. Nazarova O.A., Shutemova E.A., Fomin F.Yu., Kadnikova Yu. V., Kelesh M.V. Neyrogumoral’naya regulyatsiya u pozhilykh bol’nykh arterial’noy gipertenziey s razlichnymi tipami remodelirovaniya miokarda [Neurohumoral Regulation in Older Hypertensive Patients with Different Types of Myocardial Remodelling]. Vestnik aritmologii, 2005, no. 40, pp. 45–48.
    
37. Krivoshchekov S.G., Suvorova I.Yu., Shevchenko I.V., Baranov V.I. Kliniko-fiziologicheskie aspekty remodelirovaniya miokarda levogo zheludochka pri gipertonicheskoy bolezni [Clinical and Physiological Aspects of Left Ventricular Remodelling in Arterial Hypertension]. Vestnik Tyumenskogo gosudarstvennogo universiteta, 2015, no. 3, pp. 183–199.