Molecular basis of amyloid deposition in myocardium: not only ATTR and AL. Case report
S. E. Andreeva,
P. P. Snetkov,
Yu. A. Vakhrushev,
I. A. Piankov,
O. O. Yaznevich,
M. A. Bortsova,
S. N. Morozkina,
A. V. Kajava,
A. A. Kostareva,
M. V. Uspenskaya https://doi.org/10.18705/2311-4495-2022-9-6-26-35
Abstract
Alterations in the proteostasis network and accumulation of misfolded protein aggregates — is one of the new pathogenesis concepts of chronic heart failure. We hypothesis in addition to well-known transthyretin (ATTR) and AL-amyloidosis some patients may represent amyloid lesion in myocardium came from undescribed amyloidogenic precursors due to misfolding of myocardial structural proteins.
Here, we report on the case of patient with hypertrophic and restrictive phenotype of cardiomyopathy, biventricular heart failure, considered for heart transplant, and excluded known types of amyloidosis. Genetic testing revealed extended deletion in the gene of giant protein titin (TTN).
We present with the use of bioinformatic analysis and molecular modeling how this mutation could lead to unfolding of corresponding protein and open its amyloidogenic motifs for intermolecular interactions, therefore, provide amyloidogenic ability. This data enables in more detail to decipher the pathogenesis of chronic heart failure on the background of cardiomyopathy, planning further studies for development of personalized risk profiling in different types of amyloidosis and elaborate more personalized treatment approach for such patients in the future.
Keywords
amyloid,
bioinformatic analysis,
chronic heart failure,
molecular modeling,
myocardium,
proteostasis,
titin,
TTN
Supporting agencies: The work was carried out with the financial support of the Russian Science Foundation (project No. 21-74-20093).
About the Authors
S. E. Andreeva
Almazov National Medical Research Centre
Russian Federation
Russian Federation
Sofiya E. Andreeva, postgraduate student, cardiologist, research laboratory assistant, World-Class Research Centre for Personalized Medicine
Saint Petersburg
P. P. Snetkov
ITMO University
Petr P. Snetkov, PhD, senior engineer, Center of Chemical Engineerin
Saint Petersburg
Yu. A. Vakhrushev
Almazov National Medical Research Centre
Yurii A. Vakhrushev, research assistant, Research Laboratory of Molecular and Cellular Modeling and Gene Therapy
Saint Petersburg
I. A. Piankov
ITMO University
Ivan A. Piankov, PhD student, ChemBio cluster, engineer of International Scientific and Research Institute of Bioengineering
Saint Petersburg
O. O. Yaznevich
Almazov National Medical Research Centre
Oksana O. Yaznevich, cardiologist, Cardiology Department
Saint Petersburg
M. A. Bortsova
Almazov National Medical Research Centre
Mariya A. Bortsova, head of Cardiology Department
Saint Petersburg
S. N. Morozkina
ITMO University
Svetlana N. Morozkina, PhD, Associate Professor, leading researcher, Center for Chemical Engineering
Saint Petersburg
A. V. Kajava
Montpellier Cell Biology Research Center
France
France
Andrey V. Kajava, PhD, Professor, head of Structural Bioinformatics and Molecular Modeling group
Montpellier
A. A. Kostareva
Almazov National Medical Research Centre
Anna A. Kostareva, D.M.Sc., PhD, Associate Professor, head of the Institute of Molecular Biology and Genetics
Akkuratova str., 2, Saint Petersburg, 197341
M. V. Uspenskaya
ITMO University, Saint Petersburg
Mayya V. Uspenskaya, D.Sc, Professor, Head of Chemical Engineering Сenter, Head of Gazprom NeftITMO Research Center, Head of Research Institute Bioengineering
Saint Petersburg
References
1.
Review
For citations:
Andreeva S.E., Snetkov P.P., Vakhrushev Yu.A., Piankov I.A., Yaznevich O.O., Bortsova M.A., Morozkina S.N., Kajava A.V., Kostareva A.A., Uspenskaya M.V. Molecular basis of amyloid deposition in myocardium: not only ATTR and AL. Case report. Translational Medicine. 2022;9(6):26-35. (In Russ.) https://doi.org/10.18705/2311-4495-2022-9-6-26-35
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