Effect of induced hyperhomocysteinemia on cardiomyocytes under the experimental conditions
Authors:
M. Kovalská 1*; L. Kovalská 2; P. Kaplán 3; M. Kmeťová 3; M. Furjelová 1,3; K. Jurková 1,3; M. Adamkov 1; I. Malachovský 2; Z. Tatakrová 3
Authors place of work:
Ústav histológie a embryológie, Jesseniova lekárska fakulta v Martine, Univerzita Komenského v Bratislave, Slovensko
1; Klinika stomatológie a maxilofaciálnej chirurgie, Univerzitná nemocnica Martin, Martin, Slovensko
2; Ústav lekárskej biochémie, Jesseniova lekárska fakulta v Martine, Univerzita Komenského v Bratislave, Slovensko
3
Published in the journal:
Klin. Biochem. Metab., 22 (43), 2014, No. 2, p. 81-86
Summary
Objective:
Numerous clinical and experimental studies have noticed correlation between the occurrence of clinical effects on vascular genesis and plasma level of homocysteine (Hcy). In general, elevated level of circulating plasma homocysteine is considered as an independent risk factor for occurrence of vascular pathology. Over getting of its risk-free value can lead to increased risk of myocardial infarction up to three times. We investigated the effect of hHcy (hyperhomocysteinemia) on associated changes in MAPK/ERK (Mitogen Activated Protein Kinase/extracellular signal-regulated kinases) pathway in cardiomyocytes.
Design:
Experimental.
Material and methods:
For our experiments we used adult rats (male) Wistar. Their hearts were exteriorized in sterile conditions. The tissues were used to prepare homogenates or for immunohistological analysis. Second group of animals was subcutaneously administered by Hcy in an amount of 0.45 µmol/g of each animal twice a day during the 14-days before the experiment. After this time period the hearts were exteriorized under the same conditions as the previous group. The hearts were then connected to the Langendorff perfusion system.
Results:
In our experiments we have observed significant changes in contractility of cardiomyocytes in Hcy group. The values of left ventricular (LV) speed contractility assessments in contraction (+LV dP/dt) and relaxation (-LV dP/dt) decreased in 30.94% and in 17.42%, respectively. We have also noticed significant changes between the control group and the Hcy group in increase of the p-ERK protein levels to 143% (p<0.05) in Hcy group, which correlated well with immunohistochemical analysis.
Conclusion:
Chemically-induced 14-day hHcy can affect cardiomyocytes and thereby increase the risk of heart damage.
Key words:
heart stroke, homocysteine, hyperhomocysteinemia , MAPK.
Zdroje
1. Humphrey, L. L., Fu, R., Rogers, K., Freeman, M., Helfand, M. Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis. Mayo. Clin. Proc., 2008, 83(11), p. 1203-12.
2. Vizzardi, E., Bonadei, I., Zanini, G., et al. Homocysteine and heart failure: an overview. Recent Pat. Cardiovasc. Drug Discov., 2009, 4(1), p. 15-21.
3. Kolling, J., Scherer, E. B., da Cunha, A. A., da Cunha, M. J., Wyse, A. T. Homocysteine induces oxidative-nitrative stress in heart of rats: prevention by folic acid. Cardiovasc. Toxicol., 2011, 11(1), p. 67-73.
4. Šamudovská, K., Podracká Ľ. Homocysteín ako vaskulárny toxín. Interná med., 2009, 9(11), p. 522-526.
5. Poddar, R., Paul, S. Novel crosstalk between ERK MAPK and p38 MAPK leads to homocysteine-NMDA receptor-mediated neuronal cell death. J Neurochem., 2013, 124(4), p. 558-70.
6. Kénina, V., Auce, P., Priede, Z., Millers, A., Smeltere, E. Homocysteine, Atherothrombosis, and Stroke. Neurologijos seminarai. 2009, 13(41), p. 139–142.
7. Čaprda, M., Rašlová, K. Súčasný pohľad na homocysteín vo svete poznatkov z klinických štúdii. Interná med., 2006, 6, p. 344-347.
8. Devlin, A. M, Arning, E., Bottiglieri, T., Faraci, F. M., Rozen, R., Lentz, S. R. Effect of Mthfr genotype on diet-induced hyperhomocysteinemia and vascular function in mice. Blood, 2004, 103, p. 2624-2629.
9. Rowan, E. N., Dckinson, H. O., Stephens, S., Ballard, C., Kalaria, R., Kenny, R. A. Homocysteine and post-stroke cognitive decline. Age and Ageing, 2007, 36(3), p. 339-343.
10. Matté, C., Mussulini, B. H. M., Santos, T. M., et al. Hyperhomocysteinemia reduces glutamate uptake in parietal cortex of rats. Int. J Dev. Neurosci., 2010, 28(2), p. 183-187.
11. Kovalská, M., Kovalská, L., Furjelová, M., Adamkov, M., Lehotský, J. Indukovaná hyperhomocysteinémia a ischemické poškodenie mozgu. Slovenský lekár, 2012, 22(36), p. 46-51.
12. Lee, C. H., Yoo, K. Y., Park, O. K. et al. Phosphorylated Extracellular Signal-Regulated Kinase 1/2 Immunoreactivity and Its Protein Levels in the Gerbil Hippocampus during Normal Aging. Mol. Cells., 2010, 29, p. 373-378.
13. Tatarkova, Z., Engler, I., Calkovska, A. et al. Effect of long-term normobaric hypoxia on oxidative stress in mitochondria of the guinea pig brain. Neurochem. Res., 36, p. 1475–1481.
14. Kovalska, M., Kovalska, L., Pavlikova, M. et al. Intracellular Signaling MAPK Pathway After Cerebral Ischemia–Reperfusion Injury. Neurochem. Res., 2012, 37, p. 1568–1577.
15. Martins, P. J. F, Galdieri, L. C., Souza, F. G. et al. Physiological variation in plasma total homocysteineconcentrations in rats. Life Sci., 2005, 76, p. 2621–2629.
16. Zhang, J., Bian, H. J., Li, X. X. et al. P. ERK-MAPK Signaling Opposes Rho-Kinase to Reduce Cardiomyocyte Apoptosis in Heart Ischemic Preconditioning. Mol. Med., 2010, 16(7-8), p. 307-315.
17. Yue, T. L., Wang, C., Gu, J. L. et al. Inhibition of extracellular signal-regulated kinase enhances ischemia/reoxygenation-induced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart. Circ. Res., 2000, 86, p. 692–699.
18. Mudd, S. H., Levy, H.L., Skovby, F. Disorders of transsulfuration. In C. R. Scriver, A. L. Beaudet, W. S. The metabolic and molecular basis of inherited disease. New York: McGraw-Hill, 2001, 2, p. 1279- 1327.
19. Miller, A., Mujumdar, V., Palmer, L., Bower, J. D., Tyagi, S. C. Reversal of endocardial endothelial dysfunction by folic acid in homocysteinemic hypertensive rats. Am. J Hypertens., 2002, 15, p. 157- 163.
20. Moshal, K. S., Metreveli, N., Frank, I., Tyagi, S. C. Mitochondrial MMP activation, dysfunction and arrhythmogenesis in hyperhomocysteinemia. Curr. Vasc. Pharmacol., 2008, 6(2), p. 84-92.
21. Balakumar, P., Harsimran, S., Snigh, M., Anad-Srivastava, M. B. The impairment of preconditioning-mediated cardioprotection in pathological conditions. Pharmacol. Res., 2009, 60, p. 18-23.
22. Balakumar, P., Rohilla, A., Snigh, G., Snigh, K., Snigh, M. Modulation of cardioprotective effect of ischemic pre- and postconditioning in the hyperhomocysteinemic rat heart. Methods Find Exp. Clin. Pharmacol., 2009, 31(2), p. 71-79.
23. Snigh, G., Rohilla, A., Snigh, M., Balakumar, P. The possible Role of JAK-2 in Attenuated Cardioprotective Effect of Ischemic Preconditioning in Hyperhomocysteinemic Rat Hearts. Yakugaku Zasshi, 2009, 129(5), p. 523- 535.
24. Herrmann, M., Muller, S., Kindermann, I. et al. Plasma B vitamins and their relation to the severity of chronic heart failure. Am. J. Clin. Nutr., 2007, 85, p. 117-123.
25. Witte KK, Nikitin NP, Parker AC, et al. The effect of micronutrient supplementation on quality-of-life and left ventricular function in elderly patients with chronic heart failure. Eur. Heart J., 2005, 26, p. 2238-2244.
Štítky
Clinical biochemistry Nuclear medicine Nutritive therapistČlánok vyšiel v časopise
Clinical Biochemistry and Metabolism
2014 Číslo 2
Najčítanejšie v tomto čísle
- Clinical Problems of IgM Monoclonal Gammapathies
- Risk factors of Asymptomatic (Smoldering) Multiple Myeloma
- Diagnosis and stratification of systemic AL amyloidosis in the light of the 2013 Czech Myeloma Group recommendation
- The Standard of Analytical Quality of Glucometers