Immunopathological reactions, endothelial dysfunction and pathological angiogenesis as independent mechanisms of maladaptive left ventricular remodeling in ischemic and nonischemic heart failure patients

Authors

  • O. V. Rasputniak SI “National M. Amosov Institute of Cardiovascular Surgery Affiliated to National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine
  • T. I. Havrylenko SI “National Scientific Center “Institute of Cardiology named after M. D. Strazhesko” of the NAMS of Ukraine, Kyiv, Ukraine
  • K. V. Rudenko SI “National M. Amosov Institute of Cardiovascular Surgery Affiliated to National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine
  • N. O. Ryzhkova SI “National Scientific Center “Institute of Cardiology named after M. D. Strazhesko” of the NAMS of Ukraine, Kyiv, Ukraine
  • O. A. Pidhaina SI “National Scientific Center “Institute of Cardiology named after M. D. Strazhesko” of the NAMS of Ukraine, Kyiv, Ukraine
  • O. V. Rybakova SI “National M. Amosov Institute of Cardiovascular Surgery Affiliated to National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine
  • V. P. Zalevskyi SI “National M. Amosov Institute of Cardiovascular Surgery Affiliated to National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine
  • О. M. Lomakovskyi SI “National Scientific Center “Institute of Cardiology named after M. D. Strazhesko” of the NAMS of Ukraine, Kyiv, Ukraine

DOI:

https://doi.org/10.14739/2310-1210.2021.2.211951

Keywords:

heart failure, left ventricular remodeling, pathological angiogenesis, TNF-alpha, VEGF, endothelin-1

Abstract

Regardless of the great progress in studying the heart failure (HF) pathophysiology, the question about involvement of immune cells activation, systemic inflammation, inflammatory cytokine dysregulation and endothelial dysfunction in maladaptive left ventricular (LV) remodeling in ischemic and nonischemic HF patients is still open to discussion.

The aim was to study the characteristics of immunopathological reactions (immunoinflammatory and autoimmune), endothelial dysfunction and pathologic angiogenesis in maladaptive LV remodeling in ischemic and nonischemic HF patients.

Materials and methods. A total of 20 healthy volunteers, 31 ischemic HF patients (group 1) and 43 nonischemic HF patients (group 2) were enrolled in the study. All the patients underwent coronarography, ventriculography, echocardigraphic examination. The main lymphocyte subset counts (flow cytometry), serum concentration of C-reactive protein (CRP), vascular endothelial growth factor A (VEGF), TNFα, endothelin-1 (enzyme-linked immunosorbent assay (ELISA)), autoantibodies to myocardium and vessels were detected.

Results. Regardless of the HF etiology, all the examined patients demonstrated echocardiographic features of maladaptive LV remodeling and severe intracardiac hemodynamic disorders that was associated with immune system activation, namely increased total and subset lymphocyte counts, chronic systemic inflammation (CRP), autoimmune process with an increase in autoantibodies to myocardium and vessels, and endothelial dysfunction (increased endothelin-1 and VEGF). Under-expression of TNF-α combined with over-expression of VEGF seemed to indicate pathological angiogenesis in ischemic and nonischemic HF patients

Conclusions. Significantly increased VEGF levels in heart failure patients can be considered as additional integral key marker of immune inflammation, endothelial dysfunction and pathological angiogenesis and may indicate maladaptive cardiac remodeling in severe heart failure.

Author Biographies

O. V. Rasputniak, SI “National M. Amosov Institute of Cardiovascular Surgery Affiliated to National Academy of Medical Sciences of Ukraine”, Kyiv

MD, PhD, Cardiologist of the Department of Surgical Arrhythmias Treatment

T. I. Havrylenko, SI “National Scientific Center “Institute of Cardiology named after M. D. Strazhesko” of the NAMS of Ukraine, Kyiv

PhD, DSc, Professor, Head of the Department of Immunology and Biochemistry

K. V. Rudenko, SI “National M. Amosov Institute of Cardiovascular Surgery Affiliated to National Academy of Medical Sciences of Ukraine”, Kyiv

MD, PhD, DSc, Professor, Deputy Director for Medical Coordination

N. O. Ryzhkova, SI “National Scientific Center “Institute of Cardiology named after M. D. Strazhesko” of the NAMS of Ukraine, Kyiv

MD, PhD, Senior Researcher of the Department of Immunology and Biochemistry

O. A. Pidhaina, SI “National Scientific Center “Institute of Cardiology named after M. D. Strazhesko” of the NAMS of Ukraine, Kyiv

MD, PhD, Senior Researcher of the Department of Immunology and Biochemistry

O. V. Rybakova, SI “National M. Amosov Institute of Cardiovascular Surgery Affiliated to National Academy of Medical Sciences of Ukraine”, Kyiv

MD, PhD, Honored Worker of Science and Technology of Ukraine

V. P. Zalevskyi, SI “National M. Amosov Institute of Cardiovascular Surgery Affiliated to National Academy of Medical Sciences of Ukraine”, Kyiv

MD, Head of the Department of Surgical Arrhythmias Treatment

О. M. Lomakovskyi , SI “National Scientific Center “Institute of Cardiology named after M. D. Strazhesko” of the NAMS of Ukraine, Kyiv

MD, PhD, Senior Researcher of the Department of Atherosclerosis and Chronic Ischemic Cardiovascular Disease

References

Voronkov, L. H., Amosova, K. M., Dziak, H. V., Zharinov, O. Y., Kovalenko, V. M., Korkushko, O. V., Nesukai, O. H., Sychov, O. S., Rudyk, Yu. S., & Parkhomenko, O. M. (2017). Rekomendatsii Asotsiatsii kardiolohiv Ukrainy z diahnostyky ta likuvannia khronichnoi sertsevoi nedostatnosti (2017) [Guidelines of the Ukrainian Association of Cardiology for the Diagnosis and Treatment of Chronic Heart Failure (2017)]. Sertseva nedostatnist ta komorbidni stany, (1, dodatok 1), 1-66. [in Ukranian].

Ponikowski, P., Voors, A. A., Anker, S. D., Bueno, H., Cleland, J., Coats, A., Falk, V., González-Juanatey, J. R., Harjola, V. P., Jankowska, E. A., Jessup, M., Linde, C., Nihoyannopoulos, P., Parissis, J. T., Pieske, B., Riley, J. P., Rosano, G., Ruilope, L. M., Ruschitzka, F., Rutten, F. H., … ESC Scientific Document Group. (2016). 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal, 37(27), 2129-2200. https://doi.org/10.1093/eurheartj/ehw128

Piepoli, M. F., Hoes, A. W., Agewall, S., Albus, C., Brotons, C., Catapano, A. L., Cooney, M. T., Corrà, U., Cosyns, B., Deaton, C., Graham, I., Hall, M. S., Hobbs, F., Løchen, M. L., Löllgen, H., Marques-Vidal, P., Perk, J., Prescott, E., Redon, J., Richter, D. J., … ESC Scientific Document Group. (2016). 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). European Heart Journal, 37(29), 2315-2381. https://doi.org/10.1093/eurheartj/ehw106

Konstam, M. A., Kramer, D. G., Patel, A. R., Maron, M. S., & Udelson, J. E. (2011). Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment. JACC: Cardiovascular Imaging, 4(1), 98-108. https://doi.org/10.1016/j.jcmg.2010.10.008

Frieler, R. A., & Mortensen, R. M. (2015). Immune Cell and Other Noncardiomyocyte Regulation of Cardiac Hypertrophy and Remodeling. Circulation, 131(11), 1019-1030. https://doi.org/10.1161/CIRCULATIONAHA.114.008788

King, M., Kingery, J., & Casey, B. (2012). Diagnosis and evaluation of heart failure. American Family Physician, 85(12), 1161-1168.

Heusch, G., Libby, P., Gersh, B., Yellon, D., Böhm, M., Lopaschuk, G., & Opie, L. (2014). Cardiovascular remodelling in coronary artery disease and heart failure. The Lancet, 383(9932), 1933-1943. https://doi.org/10.1016/S0140-6736(14)60107-0

Hilfiker-Kleiner, D., Landmesser, U., & Drexler, H. (2006). Molecular Mechanisms in Heart Failure. Journal of the American College of Cardiology, 48(9. Suppl. A), A56-A66. https://doi.org/10.1016/j.jacc.2006.07.007

da Lus, P. L., Libby, P., Laurindo, F. R. M., & Chagas, A. C. P. (2018). Endothelium and Cardiovascular Diseases. Vascular Biology and Clinical Syndromes. Academic Press.

Premer, C., Kanelidis, A. J., Hare, J. M., & Schulman, I. H. (2019). Rethinking Endothelial Dysfunction as a Crucial Target in Fighting Heart Failure. Mayo Clinic Proceedings: Innovations, Quality & Outcomes, 3(1), 1-13. https://doi.org/10.1016/j.mayocpiqo.2018.12.006

Azevedo, P. S., Polegato, B. F., Minicucci, M. F., Paiva, S. A., & Zornoff, L. A. (2016). Cardiac Remodeling: Concepts, Clinical Impact, Pathophysiological Mechanisms and Pharmacologic Treatment. Arquivos Brasileiros de Cardiologia, 106(1), 62-69. https://doi.org/10.5935/abc.20160005

Evora, P. R., Nather, J., Tubino, P. V., Albuquerque, A. A., Celotto, A. C., & Rodrigues, A. J. (2013). Curbing Inflammation in the Ischemic Heart Disease. International Journal of Inflammation, 2013, Article 183061. https://doi.org/10.1155/2013/183061

Zhang, Y., Bauersachs, J., & Langer, H. F. (2017). Immune mechanisms in heart failure. European Journal of Heart Failure, 19(11), 1379-1389. https://doi.org/10.1002/ejhf.942

Ambrosova, T. N. (2013). Rol' tsitokinovoi sistemy v formirovanii khronicheskoi serdechnoi nedostatochnosti [Role of cytokine system on the chronic heart failure]. Eksperymentalna i klinichna medytsyna, (4), 61-67. [in Russian].

Heba, G., Krzemiński, T., Porc, M., Grzyb, J., & Dembińska-Kieć, A. (2001). Relation between expression of TNF alpha, iNOS, VEGF mRNA and development of heart failure after experimental myocardial infarction in rats. Journal of Physiology and Pharmacology, 52(1), 39-52.

Gavrilenko, T. I., Ryzhkova, N. A., & Parkhomenko, A. N. (2011). Sosudistyi endotelial'nyi faktor rosta v klinike vnutrennikh zabolevanii i ego patogeneticheskoe znachenie [Vascular endothelial growth factor in the clinic of internal diseases and its pathogenetic value]. Ukrainskyi kardiolohichnyi zhurnal, (4), 87-95. [in Russian].

Mangіliova, T. A. (2012). Sistema sosudistogo endotelial'nogo faktora rosta i arterial'naya gipertenziya [Vascular endothelial growth factor system and arterial hypertension]. Sertse i sudyny, (4), 107-115. [in Russian].

Libby, P. (2012). Inflammation in Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(9), 2045-2051. https://doi.org/10.1161/ATVBAHA.108.179705

Hofmann, U., & Frantz, S. (2015). Role of Lymphocytes in Myocardial Injury, Healing, and Remodeling After Myocardial Infarction. Circulation Research, 116(2), 354-367. https://doi.org/10.1161/CIRCRESAHA.116.304072

Zhao, T., Zhao, W., Chen, Y., Liu, L., Ahokas, R. A., & Sun, Y. (2013). Differential expression of vascular endothelial growth factor isoforms and receptor subtypes in the infarcted heart. International Journal of Cardiology, 167(6), 2638-2645. https://doi.org/10.1016/j.ijcard.2012.06.127

Huusko, J., Merentie, M., Dijkstra, M. H., Ryhänen, M. M., Karvinen, H., Rissanen, T. T., Vanwildemeersch, M., Hedman, M., Lipponen, J., Heinonen, S. E., Eriksson, U., Shibuya, M., & Ylä-Herttuala, S. (2010). The effects of VEGF-R1 and VEGF-R2 ligands on angiogenic responses and left ventricular function in mice. Cardiovascular Research, 86(1), 122-130. https://doi.org/10.1093/cvr/cvp382

Ramji, D. P., & Davies, T. S. (2015). Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets. Cytokine & Growth Factor Reviews, 26(6), 673-685. https://doi.org/10.1016/j.cytogfr.2015.04.003

Libby, P., Bornfeldt, K. E., & Tall, A. R. (2016). Atherosclerosis: Successes, Surprises, and Future Challenges. Circulation Research, 118(4), 531-534. https://doi.org/10.1161/CIRCRESAHA.116.308334

Dati, F., & Metzmann, E. (2007). Belki. Laboratornye testy i klinicheskoe primenenie [Proteins. Laboratory Testing and Clinical Use]. Labora. [in Russian].

Kay, M. (2013). Physiologic Autoantibody and Immunoglobulin Interventions During Aging. Current Aging Science, 6(1), 56-62. https://doi.org/10.2174/1874609811306010008

Yakobysiak, M. (2004). Imunolohiia [Immunology]. Nova knyha. [in Ukranian].

Alem, M. M. (2019). Endothelial Dysfunction in Chronic Heart Failure: Assessment, Findings, Significance, and Potential Therapeutic Targets. International Journal of Molecular Sciences, 20(13), Article 3198. https://doi.org/10.3390/ijms20133198

Zheng, W., Seftor, E. A., Meininger, C. J., Hendrix, M. J., & Tomanek, R. J. (2001). Mechanisms of coronary angiogenesis in response to stretch: role of VEGF and TGF-β. American Journal of Physiology. Heart and Circulatory Physiology, 280(2), H909-H917. https://doi.org/10.1152/ajpheart.2001.280.2.H909

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Published

2021-04-16

How to Cite

1.
Rasputniak OV, Havrylenko TI, Rudenko KV, Ryzhkova NO, Pidhaina OA, Rybakova OV, Zalevskyi VP, Lomakovskyi ОM. Immunopathological reactions, endothelial dysfunction and pathological angiogenesis as independent mechanisms of maladaptive left ventricular remodeling in ischemic and nonischemic heart failure patients. Zaporozhye Medical Journal [Internet]. 2021Apr.16 [cited 2024Nov.24];23(2):175-83. Available from: http://zmj.zsmu.edu.ua/article/view/211951

Issue

Vol. 23 No. 2 (2021)

Section

Original research

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