Marker profile of myocardial remodeling in different etiopathogenetic forms of arterial hypertension in the experiment
DOI:
https://doi.org/10.14739/2310-1237.2020.2.212721Keywords:
ventricular remodeling, myocardium, left ventricle, biomarkers, annexin V, titin, cardiotrophin-1, type I collagen, morphodensitometry, rats, hypertensionAbstract
The aim was to determine the morphodensitometric parameters of cardiomyocytes and features of the marker profile of remodeling in the left ventricular myocardium of rats with experimental hypertension of different etiopathogenetic forms.
Materials and methods. The experiment was conducted on 20 male Wistar rats and 10 SHR which were divided into two groups of 10 animals each: the 1st –control; the 2nd – rats of the SHR line (EAH); the 3rd – 10 male Wistar rats with endocrine-salt arterial hypertension. Systolic and diastolic BP levels were measured in all the rats using the system of non-invasive arterial pressure measurement BP-2000. The objects of the study were myocardial sections in which the content of immunoreactive material to remodeling markers (cardiotrophin-1, titin, collagen type I, annexin V) was determined by the immunofluorescent method, titin / collagen ratio was calculated, the average linear size of cardiomyocyte nuclei, their density, RNA concentrations in the nucleus and cytoplasm were determined by morphodensitometric method.
Results. Arterial hypertension, regardless of its etiopathogenetic form, is characterized by an increase in the number of cardiomyocyte nuclei with an increase in their size, decrease in the density and decrease in their RNA concentration against increase in the cytoplasm. In rats with EAH, the content of cardiotrophin-1 was higher than the control by 27 %, and in ESAH by 80 %. Titin levels were 12% higher in EAH and 46 % in ESAH. The collagen type I content of EAH was higher than the control by 49 %, while in the group with ESAH by 68 %. EAH rats had a higher annexin V content by 58 %, while ESAH – 64 %. The ratio of the content of titin and type I collagen in control rats was 1.01, in rats with EAH decreased to 0.76, while in rats ESAH it was 1.3.
Conclusions. The formation of arterial hypertension, regardless of its etiopathogenetic form, leads to the development of pathological myocardial remodeling, as indicated by increased heart mass and specific gravity, changes in the cytoarchitectonics of cardiomyocytes, the development of polymorphism of their nuclei with increasing size against increasing of its number with nuclear dysfunction. The marker profile of myocardial remodeling in rats with essential hypertension is characterized by a moderate increase in cardiotrophin-1 and titin, with a significant increase in collagen type I and annexin V, which in combination with a low ratio of titin / collagen type indicates fibrosis with increased myocardial stiffness and the development of hypertrophic-fibrous type of myocardial remodeling with moderate apoptosis. In rats with endocrine-salt arterial hypertension, the marker profile of myocardial remodeling is characterized by a significant increase in all 4 immunohistochemical markers of remodeling, moderate fibrosis and an increase in the titin / collagen ratio, which is characteristic of hypertrophic-apoptotic type of pathological remodeling.
References
Moreno, M. U., Eiros, R., Gavira, J. J., Gallego, C., González, A., Ravassa, S., López, B., Beaumont, J., San José, G., & Díez, J. (2017). The Hypertensive Myocardium: From Microscopic Lesions to Clinical Complications and Outcomes. The Medical clinics of North America, 101(1), 43-52. https://doi.org/10.1016/j.mcna.2016.08.002
Song, K., Wang, S., Huang, B., Luciano, A., Srivastava, R., & Mani, A. (2014). Plasma cardiotrophin-1 levels are associated with hypertensive heart disease: a meta-analysis. Journal of clinical hypertension (Greenwich, Conn.), 16(9), 686-692. https://doi.org/10.1111/jch.12376
Ding, Y., Wang, Y., Jia, Q., Wang, X., Lu, Y., Zhang, A., Lv, S., & Zhang, J. (2020). Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload. International journal of hypertension, 2020, 3014693. https://doi.org/10.1155/2020/3014693
Hong, J., Chu, M., Qian, L., Wang, J., Guo, Y., & Xu, D. (2017). Fibrillar Type I Collagen Enhances the Differentiation and Proliferation of Myofibroblasts by Lowering α2β1 Integrin Expression in Cardiac Fibrosis. BioMed research international, 2017, 1790808. https://doi.org/10.1155/2017/1790808
Kabakov, A. E., & Gabai, V. L. (2018). Cell Death and Survival Assays. Methods in molecular biology, 1709, 107-127. https://doi.org/10.1007/978-1-4939-7477-1_9
Kolesnyk, Y. M., Kolesnyk, M. Y., & Abramov, A. V. (2014). Markery remodeliuvannia miokarda shchuriv pry arterialnii hipertenzii ta eksperymentalnomu tsukrovomu diabeti: rol mitokhondrialnoi dysfunktsii [Pathological remodeling of myocardium in spontaneous hypertensive rats with experimental diabetes mellitus: the role of mitochondrial dysfunction]. Fiziolohichnyi zhurnal, 60(3), 18-27. [in Ukrainian].
Kolesnyk, Y. M., Hancheva, O. V., Abramov, A. V., Ivanenko, T. V., Tyschenko, S. V., & Kuzio, N. V. (2015). Sposib modeliuvannia symptomatychnoi arterialnoi hipertenzii u dribnykh hryzuniv [Method for modeling symptomatic hypertension in rodents]. Ukraine Patent UA 102234. https://base.uipv.org/searchINV/search.php?action=viewdetails&IdClaim=217102
Verkhovna Rada of Ukraine. (2006, February 21). Pro zakhyst tvaryn vid zhorstkoho povodzhennia : zakon Ukrainy 21.02.2006 [On the Protection of Animals from Brutal Treatment (No. 3447-IV)]. https://zakon.rada.gov.ua/laws/show/3447-15?lang=en#Text
Kolesnyk, Yu. M., Kolesnyk, M. Yu., Abramov, A. V., Tumanskyi, V. O., & Hancheva, O. V. (2015). Imunohistokhimichna i morfo-densytometrychna diahnostyka patolohichnoho remodeliuvannia miokarda pry arterialnoi hipertenzii ta tsukrovomu diabeti (Metodychni rekomendatsii) [Immunohistochemical and morpho-densitometric diagnosis of pathological myocardial remodeling in hypertension and diabetes mellitus (Guidelines)]. Kyiv. [in Ukrainian].
Kolesnik, М. Yu. (2013). Osobennosti ekspressii regulyatornogo belka taitina i kollagena I tipa v miokarde spontanno gipertenzivnykh krys s eksperimental'nym sakharnym diabetom [Peculiarities of the expression of regulatory protein titin and collagen I in myocardium of spontaneously hypertensive rats with experimental diabetes mellitus]. Pathologia, (2), 31-35. [in Russian]. https://doi.org/10.14739/2310-1237.2013.2.17365
Zaitsev, V. M., Liflyandskii, V. G., & Marinkin, V. I. (2003). Prikladnaya meditsinskaya statistika [Applied Medical Statistics]. St. Petersburg: Avrora. [in Russian].
Lin, H. Y., Lee, Y. T., Chan, Y. W., & Tse, G. (2016). Animal models for the study of primary and secondary hypertension in humans. Biomedical reports, 5(6), 653-659. https://doi.org/10.3892/br.2016.784
Li, J., Kemp, B. A., Howell, N. L., Massey, J., Mińczuk, K., Huang, Q., Chordia, M. D., Roy, R. J., Patrie, J. T., Davogustto, G. E., Kramer, C. M., Epstein, F. H., Carey, R. M., Taegtmeyer, H., Keller, S. R., & Kundu, B. K. (2019). Metabolic Changes in Spontaneously Hypertensive Rat Hearts Precede Cardiac Dysfunction and Left Ventricular Hypertrophy. Journal of the American Heart Association, 8(4), e010926. https://doi.org/10.1161/JAHA.118.010926
Kosmacheva, E. D., Martirosyan, S. M., Zubareva, N. A., & Babich, A. E. (2017). Glyukokortikoidy i arterial'naya gipertenziya u retsipientov vnutrennikh organov [Glucocorticoids and arterial hypertension in internal organs recipients]. Innovative medicine of Kuban, 8(4), 60-64. [in Russian].
Frangogiannis, N. G. (2019). Cardiac fibrosis: Cell biological mechanisms, molecular pathways and therapeutic opportunities. Molecular aspects of medicine, 65, 70-99. https://doi.org/10.1016/j.mam.2018.07.001
Martínez-Martínez, E., Brugnolaro, C., Ibarrola, J., Ravassa, S., Buonafine, M., López, B., Fernández-Celis, A., Querejeta, R., Santamaria, E., Fernández-Irigoyen, J., Rábago, G., Moreno, M. U., Jaisser, F., Díez, J., González, A., & López-Andrés, N. (2019). CT-1 (Cardiotrophin-1)-Gal-3 (Galectin-3) Axis in Cardiac Fibrosis and Inflammation. Hypertension, 73(3), 602-611. https://doi.org/10.1161/HYPERTENSIONAHA.118.11874
Watanabe, T., Konii, H., & Sato, K. (2018). Emerging Roles of Cardiotrophin-1 in the Pathogenesis and Biomarker of Atherosclerosis. J, 1(1), 94-105. https://doi.org/10.3390/j1010010.
Li, L., Zhao, Q., & Kong, W. (2018). Extracellular matrix remodeling and cardiac fibrosis. Matrix biology, 68-69, 490-506. https://doi.org/10.1016/j.matbio.2018.01.013
Warren, C. M., Jordan, M. C., Roos, K. P., Krzesinski, P. R., & Greaser, M. L. (2003). Titin isoform expression in normal and hypertensive myocardium. Cardiovascular research, 59(1), 86-94. https://doi.org/10.1016/s0008-6363(03)00328-6
González, A., Ravassa, S., López, B., Moreno, M. U., Beaumont, J., San José, G., Querejeta, R., Bayés-Genís, A., & Díez, J. (2018). Myocardial Remodeling in Hypertension. Hypertension, 72(3), 549-558. https://doi.org/10.1161/HYPERTENSIONAHA.118.11125
Leung, K. (2006, February 28). 99mTc-Hydrazinonicotinamide-annexin V In Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/books/NBK23472/
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., Annicchiarico-Petruzzelli, M., Antonov, A. V., Arama, E., Baehrecke, E. H., Barlev, N. A., Bazan, N. G., Bernassola, F., Bertrand, M., Bianchi, K., Blagosklonny, M. V., … Kroemer, G. (2018). Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell death and differentiation, 25(3), 486-541. https://doi.org/10.1038/s41418-017-0012-4
Hayakawa, Y., Aoyama, T., Yokoyama, C., Okamoto, C., Komaki, H., Minatoguchi, S., Iwasa, M., Yamada, Y., Kawamura, I., Kawasaki, M., Nishigaki, K., Mikami, A., Suzuki, F., & Minatoguchi, S. (2015). High salt intake damages the heart through activation of cardiac (pro) renin receptors even at an early stage of hypertension. PloS one, 10(3), e0120453. https://doi.org/10.1371/journal.pone.0120453
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