Assessment of the severity of connexin 43 expression in the myocardium in acute ischemia in experiment
Published 2017-04-25
Keywords
- myocardial ischemia,
- connexin 43,
- pathomorphology
How to Cite
Copyright (c) 2017 Savchenko S.V., Novoselov V.P., Morozova A.S., Skrebov R.V., Grizinger V.A., Ageeva T.A., Aidagulova S.V., Erschov K.I., Voronina E.I.

This work is licensed under a Creative Commons Attribution 4.0 International License.
Abstract
Aim. The article deals with expression of connexin 43 in the myocardium in experimental modeling of acute ischemia of the heart muscle.
Methods. The results of morphodynamics analysis of acute focal myocardial damage, as well as connexin 43 expression in the intercellular contacts of the myocardium during experimental modeling of acute ischemia in laboratory animals (n=95) are presented. Acute ischemia was induced by occlusion under local hyperthermic exposure of the left coronary artery. Myocardial samples were drawn for study following the withdrawal of animals from the experiment in 1,3,6,12,18,24 hours.
Results. The expression of connexin 43 in acute ischemia in 3, 6 and 12 hours after occlusion of the left coronary artery in ischemic areas has a statistically significant difference as compared to that of the control group, p<0.00001. When comparing the expression of connexin 43 in dynamics over the duration of the ischemic myocardium after 1 hour, 3 hours, 6 and 12 hours from the start of the experiment, statistically significant differences were observed between all three groups. When analyzing the concentrations, the significance level of p in 3- and 6-hour groups amounted to 0.0041 (p<0.0041), in other cases it was equal to 0.00001 (p<0.00001). After 18 and 24 hours from the start of the experiment, due to the development of necrotic changes in the area of acute ischemia, the connexin 43 expression increased drastically, however, high levels of connexin 43 expression in these ischemic intervals seem to be associated with background necrotized impregnation of the myocardium.
Conclusion. A decrease in the level of expression of protein gap junctions of cardiac myocytes (Сх43) in acute myocardial ischemia indicates the presence of correlation between the detected connexin 43, the duration of acute occlusion of the coronary arteries and the severity of alterative changes of the heart muscle. A lowered expression of connexin 43 in the myocardium can be used in pathological studies and forensic practice to detect early ischemic damage of the heart muscle, especially in cases of sudden cardiac death.
Received 19 August 2016. Accepted 1 February 2017.
Funding: The study was completed in accordance with the research plan of Novosibirsk State Medical University.
Conflict of interest: The authors declare no conflict of interest.
Author contributions
Design philosophy; participation in experiment, microscopic study, immune histochemical study; assessment of results obtained; article writing and editing: SSV. Discussion of study design and results; article editing: NVP. Participation in experiment and microscopic study: MAS. Participation in experiment, microscopic study, immune histochemical study; assessment of results and article writing: SRV. Participation in microscopic study; assessment of results: GVA. Participation in immune histochemical study; assessment of results: ATA. Participation in microscopic study; assessment of results: ASV. Participation in experiment: EKI. Participation in immune histochemical study; assessment of results: VEI.
References
- Kaktursky L.V. Clinical morphology of acute coronary syndrome. Arkhiv patologii = Archive of pathology. 2007;69(4):16-9. (In Russ.)
- Rybakova M.G., Kuznetsova I.A., Porsukov I.A. Vestnik pediatricheskoy akademii. 2007;(7):87-9. (In Russ.)
- Rubin E., Farber J.L. Pathology. Philadelphia-New York: Lippincott-Raven Publishers; 1999. p. 577-81.
- Novoselov V.P. On some problems of regional forensic medical examination of the siberian federal district. Vestnik sudebnoy meditsiny = Journal of Forensic Medicine. 2013;2(4):5-10. (In Russ.)
- Reznik A.G., Ivanov I.N. The morphology of the myocardium in cases of death from acute forms of ischemic heart disease. Arkhiv Patologii = Archive of pathology. 2007;69(4):32-4. (In Russ.)
- Savchenko S.V. Current issues of the expert opinion about heart morphology. Vestnik sudebnoy meditsiny = Journal of Forensic Medicine. 2012;1(3):5-8. (In Russ.)
- Ershov K.I., Nogovitsin A.V., Galunskaya M.A., Seryapina A.A., Egorova K.V., Bakhareva K.I. Modification of method of myocardium ischemia / reperfusion. Medicine and Education in Siberia. Available from: http://ngmu.ru/cozo/mos/article/text_full.php?id=1411 (accessed 14.06.2016). (In Russ.)
- Nepomnyashchikh L.M. The morphogenesis of the most important general pathological processes in the heart. Novosibirsk, Nauka Publ.; 1991. 349 p. (In Russ.)
- Gennis R.B. Biomembranes. Molecular structure and function. Moscow, Mir Publ.; 1997. 419 p. (In Russ.)
- Baranova A., Ivanov D., Petrash N., Pestova A., Skoblov M., Kelmanson I., Shagin D., Nazarenko S., Geraymovych E., Litvin O., Tiunova A., Born T.L., Usman N., Staroverov D., Lukyanov S., Panchin Y. The mammalian pannexin family is homologous to the invertebrate innexin gap junction proteins. Genomics. 2004;83(4):706-16. http://dx.doi.org/10.1016/j.ygeno.2003.09.025
- Panchin Y., Kelmanson I., Matz M., Lukyanov K., Usman N., Lukyanov S. A ubiquitous family of putative gap junction molecules. Current biology. 2000;10(13):473-4.
- Rackauskas M., Neverauskas V., Skeberdis V.A. Diversity and properties of connexin gap junction channels. Medicina (Kaunas). 2010;46(1):1-12.
- Manual on immunohistochemical diagnostics of human tumors. Edited by S.V. Petrov and T.N. Richline. Kazan, DESIGNstudio "RED" Publ.; 2012. 624 p. (In Russ.)
- Dabbs D.J. Diagnostic immunohistochemistry. Elsevier Inc.; 2010. 941 р.
- Martin P.E., Blundell G., Ahmad S., Errington R.J., Evans W.H. Multiple pathways in the trafficking and assembly of connexin 26, 32 and 43 into gap junction intercellular communication channels. J Cell Sci. 2001;114(Pt 21):3845-55.
- Lampe P.D., TenBroek E.M., Burt J.M., Kurata W.E., Johnson R.G., Lau A.F. Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication. J Cell Biol. 2000;149(7):1503-12.
- VanSlyke J.K., Musil L.S. Dislocation and degradation from the ER are regulated by cytosolic stress. J Cell Biol. 2002;157(3):381-94. http://dx.doi.org/10.1083/jcb.200111045
- Laird D.W., Castillo M., Kasprzak L. Gap junction turnover, intracellular trafficking, and phosphorylation of connexin43 in brefeldin A-treated rat mammary tumor cells. J Cell Biol. 1995;131(5):1193-203.
- Musil L.S., Le A.C., VanSlyke J.K., Roberts L.M. Regulation of connexin degradation as a mechanism to increase gap junction assembly and function. J Biol Chem. 2000;275(33):25207-15.
- Antunes E., Borrecho G., Oliveira P., Brito J., Águas A., Martins dos Santos J. Immunohistochemical evaluation of cardiac connexin43 in rats exposed to low-frequency noise. Int J Clin Exp Pathol. 2013;6(9):1874-9.