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Invited researcher Sergey Mikhailovich Danilov
Contract number
14.Z50.31.0026
Time span of the project
2014-2018

As of 30.01.2020

24
Number of staff members
31
scientific publications
3
Objects of intellectual property
General information

Name of the project: Molecular mechanisms of atrial fibrillation

Strategy for Scientific and Technological Development Priority Level: в


Goals and objectives

Research directions: Research of molecular, genetic, neurohumoral, and structural predictors of development of acute arrhythmia. in particular, atrial fibrillations

Project objective: Search for molecular markers of disruptions of heart rhythm, in particular, atrial fibrillations that poses high risks of development of cerebral hemorrhage and death; development of new approaches allowing to efficiently determine patients with high risks of onset of arrhythmia and possible complications at early stages as well as finding personalized treatment plans.


The practical value of the study

  • The Laboratory has conducted a series of experiments in phenotyping of angiotensin-converting ferment. We have determined conformational differences in angiotensin-converting ferment from various human organs.
  • The Laboratory has conducted a series of experiments in biotyping of angiotensin-converting ferment that is technologically suitable for further production of preparative amounts of angiotensin-converting ferment from human heart for subsequent selection of a library of recombinant antibodies.
  • The Laboratory has conducted a series of experiments in determining expression of angiotensin-converting ferment and other biomarkers in blood and bioptates of atrial tissues in patients with various forms of atrial fibrillation and control groups.
  • We have conducted isolation of angiotensin-converting ferment from various tissues with subsequent determination of conformational fingerpringing of synthesized medications. Obtained results indicate that activity of angiotensin-converting ferment in human heart is 3 times higher than concentration of angiotensin-converting ferment in plasma and 12–15 as high as activity in lungs in kidneys.
  • Our researchers have found that «visible» activity of angiotensin-converting ferment in atria was insignificantly lower than in ventricle.
  • It has been determined that homogenates of human tissues, including various chambers of heart contain high concentration of endogenous inhibitors/effectors of angiotensin-converting ferment whose presence changes monoclonal antibodies binding against angiotensin-converting ferment «recognizing» 17 various epitopes on surfaces of molecules of human angiotensin-converting ferment.
  • We have conducted assessment of structural and hemodynamic changes of atria in patients with isolated form of atrial fibrillation, their forecasted values, determination of correlation between morphofunctional disorders and biochemical markers of inflammation and damage.
  • It has been determined that markers of myocardial damage, fibrosis and hypercoagulation are related to structural remodeling of left atrium. Increase of level of the myocardial stress marker is associated with decrease of blood flow is associated with decrease of blood flow in left auricle. Level of myocardial damage markers, left atrial dilatation, increase of mass of myocardium and Left ventricular diastolic dysfunction is associated with risk of development of cerebral hemorrhage.
  • To determine predictors of efficiency of radiofrequency ablation we have studied results of treatment. Independent predictors of development of relapse of atrial fibrillation after   radiofrequency ablation surgery are: ejection fraction (over 61,5%), Sa septal (below 1,29%), Sa anterior (below 14%), Sa posterior (below 0,87%).
  • To increase forecasting value of we have proposed a formula: Y= Const + K1× ejection fraction left ventricle + K2× SRs lateral + K3× Sa anterior, that allows, in case of usage of indicators that have the highest forecasting value, to forecast development relapse of atrial fibrillation after radiofrequency ablation with sensitivity 92% and specificity of 88% (p=0,0035).

Implemented results of research:

  • A method has been developed for assessment of risks of unfavorable cardiac events after transcutaneous coronary intervention, an application of authorship of the invention has been filed and a patent has been obtained.
  • A new method has been developed for detecting activity of angiotensin-converting ferment in heart tissues, a patent for the invention has been filed.
  • All our developments have been implemented and have been used in clinical practice in non-invasive arrhythmology and surgical treatment of combined pathology departments of the A. N. Bakulev National Medical Research Center for Cardiovascular Surgery.

Education and career development:

  • The Laboratory has conducted seminars and lecture courses for doctors – specialists in the domain of cardiology, cardiac surgery and functional diagnostics doctors («Factors of thromboembolic complications and thrombosis of cardiac cavities», «Atrial fibrillation: possibilities of personalized approach to prevention and treatment», «Structure of active center of angiotensin-converting ferment. Substrate and inhibitor specificity», «Role glycosilation and sialylation of proteins in support of their biochemmical functions»).
  • We have conducted the annual all-Russian scientific and practical school «Visualization in cardiology and cardiac surgery» (2015 – 2018), 4 schools within the 21st all-Russian congress of cardiovascular surgeons of the A. N. Bakulev National Medical Research Center for Cardiovascular Surgery with the all-Russian conference of young scientists.
  • We have conducted additional training courses: the Professional Schools for Cardiologists, Arrythmologists, Cardiovascular Surgeons and Therapists with awarding qualification certificates «Evolution and modern vision of diagnostics and treatment of ischemic heart disease» (2014), all-Russian School and Seminar «Clinical electrophysiology, interventional and surgical arrhythmology» (2015, 2016), «Modern ultrasound technologies in clinical examples and demonstrations» (2017), «Visualization in cardiology and cardiac surgery» (2018).

Other results:

Results of scientific research have been on several occasions presented at such international conferences as the annual congress of the American Heart Association (USA, 2014), the annual congress of the European Society for Vascular Surgery (France, 2017), the annual congress of the Asian Society for Cardiovascular and Thoracic Surgery (Taiwan, 2017; Russia, 2018), the European Congress in Cardiac Insufficiency (Portugal. 2017), the European Congress on Visualization (Italy, 2018), the European Meeting of Cardiologists (Italy, 2016; Spain, 2017; Germany, 2018) and others.

Collaborations: Moscow State University: joint series of experiments in fermentation and biotinylation of angiotensin-converting ferment, isolating conformational differences in angiotensin-converting ferment from various human organs, producing medication of angiotensin-converting ferment from human heart for selection of a library of recombinant antibodies

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Golukhova E.Z., Gromova O.I., Shomahov R.A., Bulaeva N.I., Bockeria L.A.
Monogenec Arrythmic Syndromes: From Molecular and Genetic Aspects to Bedside. Acta Naturae 8(2): 62–74 (2016).
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