Cytokine Profile of Myocardial Cells in Coronary Heart Disease and Ischemic Cardiomyopathy

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

In the present work, we carried out a comparative analysis of myocardial cytokine profile in patients with coronary heart disease (CHD) and in patients with ischemic cardiomyopathy (ICMP) associated with CHD. The concentrations of 41 cytokines secreted by 24-hour myocardial tissue culture intraoperatively sampled from the right atrial auricle (RAA, control) and peri-infarct left ventricular zone (PZ-LV) were determined by flow fluorimetry using a multiplex test system. The aim was to study in vitro cytokine profile of myocardial cells to search for possible predictors of adverse outcomes of surgical treatment of patients with CHD and ICMP. Myocardial secretion of proinflammatory molecules GM-CSF and IFN-γ increased significantly (up to 78-80 pg/g, p<0.05) in patients with ICMP associated with CHD in contrast to zero values in CHD. At the same time, there was a three-fold decrease in the concentration of fractalkin 3 ligand (Flt-3L; FMS-like tyrosine kinase 3 ligand). A decrease in Flt-3L secretion was observed in the PZ-LV in comparison with the RAA. In addition, compared with RAA, concentrations of fibroblast growth factor-2 (FGF-2), platelet-derived growth factor-AB/BB (PDGFAB/BB), interleukins IL-15 and IL-4, and a regulated upon activation, normal T cell expressed and secreted (RANTES; CCL5) were strongly reduced in PZ-LV myocardial tissue culture. Differences in the course of CHD and ICMP are discussed, and possible predictors of surgical treatment risk in patients of the two groups are suggested using correlation and regression analyses. Proinflammatory cytokines (IL-5, IL-6) and chemokines (Flt-3L, IL-8), as well as angiogenesis factors (VEGF) and angiostasis (IP-10), are proposed to be considered as potential markers of adverse outcome of surgical treatment of cardiovascular disease.

About the authors

A. I. Stelmashenko

Morphology and General Pathology Department, Siberian State Medical University; Laboratory of Cellular and Microfluidic Technologies, Siberian State Medical University

Email: larisalitvinova@yandex.ru
Russia, 634050, Tomsk; Russia, 634050, Tomsk

S. L. Andreev

Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: larisalitvinova@yandex.ru
Russia, 634012, Tomsk

L. S. Litvinova

Laboratory of Cellular and Microfluidic Technologies, Siberian State Medical University; Center of Immunology and Cell Biotechnology, Immanuel Kant Baltic Federal University

Author for correspondence.
Email: larisalitvinova@yandex.ru
Russia, 634050, Tomsk; Russia, 236041, Kaliningrad

V. V. Malashchenko

Center of Immunology and Cell Biotechnology, Immanuel Kant Baltic Federal University

Email: larisalitvinova@yandex.ru
Russia, 236041, Kaliningrad

N. M. Todosenko

Center of Immunology and Cell Biotechnology, Immanuel Kant Baltic Federal University

Email: larisalitvinova@yandex.ru
Russia, 236041, Kaliningrad

N. D. Gazatova

Center of Immunology and Cell Biotechnology, Immanuel Kant Baltic Federal University

Email: larisalitvinova@yandex.ru
Russia, 236041, Kaliningrad

I. А. Khlusov

Morphology and General Pathology Department, Siberian State Medical University; Laboratory of Cellular and Microfluidic Technologies, Siberian State Medical University

Email: larisalitvinova@yandex.ru
Russia, 634050, Tomsk; Russia, 634050, Tomsk

V. M. Shipulin

Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: larisalitvinova@yandex.ru
Russia, 634012, Tomsk

References

  1. Гольдберг Е.Д., Дыгай А.М., Удут В.В., Наумов С.А., Хлусов И.А. 1996. Закономерности структурной организации систем жизнеобеспечения в норме и при развитии патологического процесса. Томск. 283 с. (Gol’dberg E.D., Dygay A.M., Udut V.V., Naumov S.A., Khlusov I.A. 1996. Regularities of structural organization of life support systems in norm and in development of pathological process. Tomsk. 283 p.)
  2. Гриценко О.В., Чумакова Г.А., Шевляков И.В., Веселовская Н.Г. 2020. Внеклеточный матрикс сердца и его изменения при фиброзе миокарда. Кардиология. Т. 60. № 6. С. 107. (Gritsenko O.V., Chumakova G.A., Shevlyakov I.V., Veselovskaya N.G. 2020. Extracellular matrix of the heart and its changes in myocardial fibrosis. Kardiologiia. V. 6. № 6. P. 107.) https://doi.org/10.18087/cardio.2020.6.n773
  3. Кожевников М.Л. 2009. Морфологические признаки вероятности послеоперационного ремоделирования левого желудочка у больных с приобретенными пороками сердца. Автореф. канд. дис. Томск. 23 с. (Kozhevnikov M.L. 2009. Morphological signs of the likelihood of postoperative left ventricular remodeling in patients with acquired heart defects. PhD Thesis. Tomsk. 23 p.)
  4. Корнева Ю.С., Доросевич А.Е. 2016. Динамика морфологических изменений в пограничной зоне при организации инфаркта миокарда. Медицинский вестник Северного Кавказа. Т. 11. № 3. С. 417. (Korneva Yu.S., Dorosevich A.E. 2016. Dynamic of morphological changes in border zone during myocardial infarction organizati. Med. News of North Caucasus. V. 3. № 3. P. 417.)
  5. Москалёв А.В., Рудой А.С., Апчел В.Я. 2017. Хемокины, их рецепторы и особенности развития иммунного ответа. Вестник Российской военно-медицинской академии. Т. 2. С. 182. (Moskalev A.V., Rudoy A.S., Apchel V.Ya. 2017. Chemokines, their receptors and features of development of the immune answer. Bull. Russ. Military Med. Acad. V. 2. P. 182.)
  6. Симбирцев А.С. 2018. Цитокины в патогенезе и лечении заболеваний человека. СПб: Фолиант. 512 с. (Simbirtsev A.S. 2018. Cytokines in pathogenesis and treatment of human diseases. SPb: Foliant. 512 р.)
  7. Стельмашенко А.И., Беляева С.А. 2019. Морфологические и молекулярные предикторы повторного ремоделирования левого желудочка при ишемической кардиомиопатии. Морфологический альманах имени В.Г. Ковешникова. Т. 17. № 4. С. 71. (Stelmashenko A.I., Belyaeva S.A. 2019. Morphological and molecular predictors of left ventricular remodeling in ischemic cardiomyopathy. V.G. Koveshnikov Morphological Almanac. V. 17. № 4. P. 71.)
  8. Стельмашенко А.И., Беляева С.А., Ракина М.А., Андреев С.Л. 2020. Роль макрофагов в ремоделировании левого желудочка у пациентов с ишемической кардиомиопатией. Морфологический альманах имени В.Г. Ковешникова. Т. 18. № 4. С. 61. (Stelmashenko A.I., Belyaeva S.A., Rakina M.A., Andreev S.L. 2020. The role of macrophages in left ventricular remodeling in patients with ischemic cardiomyopathy. Koveshnikov Morphological Almanac. V. 18. № 4. P. 61.)
  9. Хамитова К.А., Чепурная А.Н., Никуличева В.И., Сафуанова Г.Ш. 2017. Содержание цитокиновых маркеров воспаления у больных при хронической сердечной недостаточности, обусловленной некоторыми кардиомиопатиями. Acta Biomed. Sci. Т. 2. № 3. С. 48. (Khamitova K.A., Chepurnaya A.N., Nikulicheva V.I., Safuanova G.Sh. 2017. Content of cytokine inflammatory markers in patients with chronic heart failure caused by cardiomyopathy. Acta Biomed. Sci. V. 2. № 3. P. 48.)
  10. Шевченко А.В., Прокофьев В.Ф., Коненков В.И., Хапаев Р.С., Нимаев В.В. 2020. Полиморфизм генов фактора роста эндотелия сосудов (VEGF) и матриксных металлопротеиназ (ММР) при первичной лимфедеме конечностей. Медицинская иммунология. Т. 22. № 3. С. 497. (Shevchenko A.V., Prokofyev V.F., Konenkov V.I., Khapaev R.S., Nimaev V.V. 2020. Polymorphism of vascular endothelial growth factor gene (VEGF) and matrix metalloproteinase (ММР) genes in primary limb lymphedema. Med. Immunol. V. 22. № 3. P. 497.) https://doi.org/10.15789/1563-0625-POV-1913
  11. Шперлинг И.Д., Аракелян Л.А. 1989. Число и размеры желудочковых кардиомиоцитов человека и количество ядер в них. Цитология. Т. 31. № 4. С. 426. (Sperling I.D., Arakelyan L.А. 1989. Number and size of human ventricular cardiomyocytes and number of nuclei in them. Cell Tiss. Biol. (Tsitologiya). V. 31. № 4. P. 426.)
  12. Юрова К.А., Хазиахматова О.Г., Малащенко В.В., Норкин И.К., Иванов П.А., Хлусов И.А., Шунькин Е.О., Тодосенко Н.М., Мелащенко Е.С., Литвинова Л.С. 2020. Клеточно-молекулярные аспекты воспаления, ангиогенеза и остеогенеза. Краткий обзор. Цитология. Т. 62. № 5. С. 305. (Yurova K.A., Khaziakhmatova O.G., Malashchenko V.V., Shunkin E.O., Todosenko N.M., Norkin I.K., Ivanov P.A., Khlusov I.A., Melashchenko E.S., Litvinova L.S. 2020. Cellular-molecular aspects of inflammation, angiogenesis and osteogenesis. A short review. Cell Tiss. Biol. (Tsitologiya). V. 62. № 5. P. 305.)
  13. Bartekova M., Radosinska J., Jelemensky M., Dhalla N.S. 2018. Role of cytokines and inflammation in heart function during health and disease. Heart Fail Rev. V. 5. P. 733.
  14. https://doi.org/10.1007/s10741-018-9716-x
  15. Berezin A.E., Berezin A.A. 2020. Adverse cardiac remodelling after acute myocardial infarction: old and new biomarkers. Disease Markers. V. 2020. P. 21 https://doi.org/10.1155/2020/1215802
  16. Boag S.E., Das R., Shmeleva E.V., Bagnall A., Egred M., Howard N., Spyridopoulos I. 2015. T lymphocytes and fractalkine contribute to myocardial ischemia/reperfusion injury in patients. J. Clin. Invest. V. 125. P. 3063. https://doi.org/10.1172/JCI80055
  17. Boren E., Gershwin M.E. 2004. Inflamm-aging: autoimmunity, and the immune-risk phenotype. Autoimmunity rev. V. 3. P. 401.
  18. Choi W., Wolber R., Gerwat W., Mann T., Batzer J., Smuda C., Liu H., Kolbe L., Hearing V.J. 2010. The fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin. J. of Cell Science. V. 123. P. 3102. https://doi.org/10.1242/jcs.064774
  19. Cojan-Minzat B.O., Zlibut A., Agoston-Coldea L. 2021. Non-ischemic dilated cardiomyopathy and cardiac fibrosis. Heart Fail. Rev. V. 26. P. 1081. https://doi.org/10.1007/s10741-020-09940-0
  20. Damås J.K., Boullier A., Wæhre T., Smith C., Sandberg W.J., Green S., Quehenberger O. 2005. Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, is elevated in coronary artery disease and is reduced during statin therapy. Arteriosclerosis Thrombosis Vascular Biol. V. 25. P. 2567. https://doi.org/10.1161/01.ATV.0000190672.36490.7b
  21. Deshmane S.L., Kremlev S., Amini S., Sawaya B.E. 2009. Monocyte chemoattractant protein-1 (MCP-1): An overview. J. Interferon Cytokine Res. V. 29. P. 313. https://doi.org/10.1089/jir.2008.0027
  22. Dor V. 1997. Left ventricular aneurysms: The endoventricular circular patch plasty. Seminars in thoracic and cardiovascular surgery. V. 9. P. 123.
  23. Felker G.M., Shaw L.K., O’Connor C.M. 2002. A standardized definition of ischemic cardiomyopathy for use in clinical research. J. Am. Coll. Cardiol. V. 39. P. 210. https://doi.org/10.1016/S0735-1097(01)01738-7
  24. Fontes J.A., Rose N.R., Čiháková D. 2015. The varying faces of IL-6: From cardiac protection to cardiac failure. Cytokine. V. 74. P. 62. https://doi.org/10.1016/j.cyto.2014.12.024
  25. Goudswaard L.J. 2019. Do the chemokines MDC and TARC contribute to obesity-related platelet hyperactivity and cardiovascular disease? Abstracts of the 1st Platelet Society Meeting. Bristol. P. 133. https://www.tandfonline.com/doi/full/10.1080/09537104.2019.1693140
  26. Henein M.Y., Vancheri S., Longo G., Vancheri F. 2022. The role of inflammation in cardiovascular disease. Int. J. Mol. Sci. V. 23. P. 12906. https://doi.org/10.3390/ijms232112906
  27. Hirota H., Yoshida K., Kishimoto T., Taga T. 1995. Continuous activation of gp130, a signal-transducing receptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice. Proc. Natl. Acad. Sci. USA. V. 92. P. 4862. https://doi.org/10.1073/pnas.92.11.486
  28. Hueso L., Ortega R., Selles F., Wu-Xiong N.Y., Ortega J., Civera M., Ascaso J.F., Sanz M.J., Real J.T., Piqueras L. 2018. Upregulation of angiostatic chemokines IP-10/CXCL10 and I-TAC/CXCL11 in human obesity and their implication for adipose tissue angiogenesis. Int. J. Obes. (Lond.). V. 42. P. 1406. https://doi.org/10.1038/s41366-018-0102-5
  29. Ibáñez B., Heusch G., Ovize M., Van de Werf F. 2015. Evolving therapies for myocardial ischemia/reperfusion injury. J. Am. College Cardiol. V. 65. P. 1454. https://doi.org/10.1016/j.jacc.2015.02.032
  30. Jiang D., Rinkevich Y. 2018. Defining skin fibroblastic cell types beyond CD90. Frontiers Cell Devel. Biol. V. 6. P.133. https://doi.org/10.3389/fcell.2018.00133
  31. Kologrivova I., Shtatolkina M., Suslova T., Ryabov V. 2021. Cells of the immune system in cardiac remodeling: Main players in resolution of inflammation and repair after myocardial infarction. Front. Immunol. V. 12. P. 664457. https://doi.org/10.3389/fimmu.2021.664457
  32. Maass D.L., White J., Horton J.W. 2005. Nitric oxide donors alter cardiomyocyte cytokine secretion and cardiac function. Crit. Care Med. V. 33. P. 2794.
  33. Menicanti L. 2002. The Dor procedure: What has changed after fifteen years of clinical practice? J. Thorac. Cardiovasc. Surg. V. 124. P. 886. https://doi.org/10.1067/mtc.2002.129140
  34. Murakami T., Iwagaki H., Saito S. 2015. Equivalence of the acute cytokine surge and myocardial injury after coronary artery bypass grafting with and without a novel extracorporeal circulation system. J. Int. Med. Res. V. 33. P. 133. https://doi.org/10.1177/147323000503300201
  35. Narasimhalu K., Ma L., De Silva D.A., Wong M.C., Chang H.M., Chen C. 2015. Elevated platelet-derived growth factor AB/BB is associated with a lower risk of recurrent vascular events in stroke patients. Int. J. Stroke. V. 10. P. 85. https://doi.org/10.1111/ijs.1235
  36. Prabhu S.D., Frangogiannis N.G. 2016. The biological basis for cardiac repair after myocardial infarction: From inflammation to fibrosis. Circ. Res. V. 119. P. 91. https://doi.org/10.1161/CIRCRESAHA.116.303577
  37. Ridker P.M., Everett B.M., Thuren T., MacFadyen J.G., Chang W.H., Ballantyne C., Fonseca F., Nicolau J., Koenig W., Anker S., Kastelein J.P., Cornel Jan H., Pais P., Pella D., Genest J. et al. 2017. Antiinflammatory therapy with canakinumab for atherosclerotic disease. V. 377. P. 1119.
  38. https://doi.org/10.1056/NEJMoa1707914
  39. Robba C., Battaglini D., Pelosi P., Rocco P.R.M. 2020. Multiple organ dysfunction in SARS-CoV-2: MODS-CoV-2. Expert Rev. Respir. Med. V. 14. P. 865. https://doi.org/10.1080/17476348.2020.1778470
  40. Shvangiradze T.A., Bondarenko I.Z., Troshina E.A., Shestakova M.V., Ilyin A.V., Nikankina L.V., Karpukhin A.V., Muzaffarova T.A., Kipkeeva F.M., Grishina K.A., Kuzevanova A.Y. 2016. Profile of micrornas associated with coronary heart disease in patients with type 2 diabetes. Obesity Metabolism. V. 13. P. 34. https://doi.org/10.14341/omet2016434-38
  41. Spray L., Park C., Cormack S., Mohammed A., Panahi P., Boag S., Bennaceur K., Sopova K., Richardson G., Stangl V., Rech L., Rainer P., Ramos G., Hofmann U., Stellos K. et al. 2021. The fractalkine receptor CX3CR1 links lymphocyte kinetics in CMV-seropositive patients and acute myocardial infarction with adverse left ventricular remodeling. Front. Immunol. V. 12. P. 605857. https://doi.org/10.1007/s00109-005-0035-z
  42. Timonen P., Magga J., Risteli J., Punnonen K., Vanninen E., Turpeinen A., Tuomainen P., Kuusisto J., Vuolteenaho O., Peuhkurinen K. 2008. Cytokines, interstitial collagen and ventricular remodelling in dilated cardiomyopathy. Int. J. Cardiol. V. 124. P. 293. https://doi.org/10.1016/j.ijcard.2007.02.004
  43. Urazova O., Chumakova S., Vins M., Maynagasheva E., Shipulin V., Pryahin A., Poletika V., Kononova T., Kolobovnikova Y., Novitskiy V. 2019. Characteristics of humoral regulation of differentiation of bone marrow monocyte subpopulations in patients with ischemic cardiomyopathy. Int. J. Biomed. V. 9. P. 91. https://doi.org/10.21103/Article9(2)_OA1
  44. Van den Broek L.J., Kroeze K.L., Waaijman T., Breetveld M., Sampat-Sardjoepersad S.C., Niessen F.B., Gibbs S. 2014. Differential response of human adipose tissue-derived mesenchymal stem cells, dermal fibroblasts, and keratinocytes to burn wound exudates: potential role of skin-specific chemokine CCL27. Tiss. Eng. Part 1. V. 20. P. 197. https://doi.org/10.1089/ten.tea.2013.0123
  45. Van der Heijden T., Bot I., Kuiper J. 2019. The IL-12 cytokine family in cardiovascular diseases. Cytokine. V. 122. P. 154. https://doi.org/10.1016/j.cyto.2017.10.010
  46. Yang X.C., Liu Y., Wang L.F., Cui L., Wang T., Ge Y.G., Zhao Z.Q. 2007. Reduction in myocardial infarct size by postconditioning in patients after percutaneous coronary intervention. J. Invasive Cardiol. V. 19. P. 424.

Supplementary files

Supplementary Files
Action
1. JATS XML
2.

Download (116KB)
3.

Download (2MB)
4.

Download (319KB)
5.

Download (122KB)
6.

Download (79KB)

Copyright (c) 2023 А.И. Стельмашенко, С.Л. Андреев, Л.С. Литвинова, В.В. Малащенко, Н.М. Тодосенко, Н.Д. Газатова, И.А. Хлусов, В.М. Шипулин

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies