Candesartan, candesartan cilexetil, resveratrol and their combinations change the amount of endothelial progenitor cells, cytogenetic and cytokinetic parameters in adipose tissue cell culture

  • A. Beliayeva “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv
  • L. Garmanchuk “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv
Keywords: Candesartan cilexetil; candesartan; resveratrol; CD117 ; CD34 ; CD117 /СD34 ; CD31 stem cells; apoptotic cells; cells with micronuclei and parameters of cell cycle.


Cardiovascular diseases are one of the most dangerous cause of mortality in many countries. At present it is important to research new methods of treatment and prevention of these diseases and create new effective and safe drugs and their combinations to decrease the evidence of cases of cardiovascular pathology. Candesartan cilexetil is an angiotensin II receptor antagonist. It’s a precursor to the active form of candesartan. These substances have a cytotoxic effect, affecting the antioxidant system. Therefore, to prevent the cytotoxic effect is the need to use antioxidants. Resveratrol is a naturally occurring polyphenol, which has positive properties on cardiovascular system. Goal. To investigate the effect of candesartan cilexetil, candesartan and antioxidant resveratrol in different doses and combinations on the number of CD117+, CD34+, CD117+/СD34+, CD31+ stem cells, on the amount of apoptotic and micronucleated cells and cell cycle parameters in vitro. Methods. We used cell culture of adipose tissue for the experiments. After incubation with studied substances, the biological characteristics of stem cells were determined. Flow cytometry method was applied to investigate the number of CD117+, CD34+, CD117+/СD34+, CD31+ stem cells, the ratio of apoptotic cells, cells with micronuclei and parameters of cell cycle in vitro. Results. Candesartan cilexetil with resveratrol and candesartan with resveratrol were effective in the stimulation of formation of endothelial progenitor cells as compared to the control and cytostatics. Candesartan cilexetil and candesartan were cytotoxic in cell culture. Resveratrol reduced the negative effects of candesartan cilexetil/candesartan in combinations. Conclusions. Complex use of candesartan cilexetil and candesartan with natural antioxidant resveratrol showed stimulating effect on differentiation of stem cells into endothelial progenitor cells, and combinations of substances were not cytotoxic.


1. Yan F., Sun X., Xu C. Protective effects of resveratrol improve cardiovascular function in rats with diabetes. Exp. Ther. Med. 2018;15:1728–1734. doi: 10.3892/etm.2017.5537.
2. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Bone marrow cells regenerate infracted myocardium. Nature. 2001; 410 (6829): 701–705.
3. Orlic, D, Hill JM, Arai A E. Stem cells for myocardial regeneration. Circulation Research. 2002; 91: 1092–1102.
4. Kladnytska L. V., Mazurkevych A. Y., Velychko S. V., Zygunova O. V. The method of obtaining the culture of stem cells from the adipose tissue of the dog. Bulletin of Sumy national agrarian University. 2016; 6 (38): 19–23.
5. Frese L, Dijkman PE, Hoerstrup SP. Adipose Tissue-Derived Stem Cells in Regenerative Medicine. Transfus Med Hemother. 2016; 43: 268–274.
6. Bunnell B, Flaat M, Gagliardi C, Patel B, Ripoll C. Adipose-derived Stem Cells: Isolation, Expansion and Differentiation. Methods. 2008; 45(2): 115–120.
7. Zhao D, Liu H, Dong P. A Meta-analysis of antihypertensive effect of telmisartan versus candesartan in patients with essential hypertension. Clin Exp Hypertens 2019;41(1):75-79.
8. De Rosa ML, Chiariello M. Candesartan improves maximal exercise capacity in hypertensives results of a randomized placebo-controlled crossover trial. J. Clin Hypertens. 2009; 11 (4): 192–200.
9. Naeshiro I, Sato K, Chatani F, Sato S. Possible mechanism for the anemia induced by candesartan cilexetil (TCV-116), an angiotensin II receptor antagonist, in rats. Europ J of Pharmacology. 1998; 354 (2/3): 179–187.
10. Adi Y. Berman, Rachel A. Motechin, Maia Y. Wiesenfeld, Marina K. Holz. The therapeutic potential of resveratrol: a review of clinical trials. NPJ Precis Oncol. 2017; 1: 35.
11. Brisdelli F, D'Andrea G, Bozzi A. Resveratrol: a natural polyphenol with multiple chemopreventive properties. Curr Drug Metab. 2009; 10 (6): 530-46.
12. Riba A., Deres L., Sumegi B., Toth K., Szabados E., Halmosi R. Cardioprotective effect of resveratrol in a postinfarction heart failure model. Oxid. Med. Cell. Longev. 2017; 2017:6819281. doi: 10.1155/2017/6819281
13. Zhigang Zhang, Li Gao, Yanyan Cheng, Jing Jiang, Yan Chen, Huijie Jiang, Hongxiang Yu, Anshan Shan, Baojing Cheng. Resveratrol, a Natural Antioxidant, Has a Protective Effect on Liver Injury Induced by Inorganic Arsenic Exposure. BioMed Research International. Volume 2014, Article ID 617202, 7 pages.
14. Alhusban A, Kozak A, Ergul A, Fagan S. AT1 receptor antagonism is proangiogenic in the brain: BDNF a novel mediator / A..The J. of Pharmacology a. Experimental Therapeutics. 2013; 344 (2): 348–359.
15. Soliman S, Ishrat T, Pillai A, Somanath P, ErgulA, El-Remessy A, Fagan S. Candesartan induces a prolonged proangiogenic effect and augments endothelium-mediated neuroprotection after oxygen and glucose deprivation: role of vascular endothelial growth factors A and B. The J. of Pharmacology a. Experimental Therapeutics. 2014; 349 (3): 444–457.
16. Campagnolo P, Hong X, di Bernardini E, Smyrnias I, Hu Y, Xu Q.Resveratrol-induced vascular progenitor differentiation towards endothelial lineage via MiR-21/Akt/β-catenin is protective in vessel graft models. PLoS One. 2015;10 (5): E0125122.
17. Wang XB, Huang J, Zou JG, Su EB, Shan QJ, Yang ZJ, Cao KJ. Effects of resveratrol on number and activity of endothelial progenitor cells from human peripheral blood. Clinical a. Experimental Pharmacology a. Physiology.2007; 34(11): 1109–1115.

Abstract views: 137
PDF Downloads: 69
How to Cite
Beliayeva, A., & Garmanchuk, L. (2019). Candesartan, candesartan cilexetil, resveratrol and their combinations change the amount of endothelial progenitor cells, cytogenetic and cytokinetic parameters in adipose tissue cell culture. Fundamental and Applied Researches in Practice of Leading Scientific Schools, 36(6), 96-99. Retrieved from