Effects of IMOD™ on angiogenesis, miR-503 and CDC25 expression levels in heart tissue of diabetic male rats

Document Type : Original Research Article

Authors

1 Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Objective: Diabetes is associated with vascular complications and impaired angiogenesis. Since angiogenesis plays a crucial role in vascular homeostasis in ischemic heart diseases, in this study, the effect of IMOD™ on miR-503 and CDC25 expression level which are altered in impaired angiogenesis were investigated in heart tissue of diabetic rats.
Materials and Methods: Forty male Wistar rats (200-250 g) were randomly classified into 4 groups: control (C), IMOD™ (I), diabetes (D), and diabetes+IMOD™ (D+I). For induction of experimental diabetes in animals, a single dose of streptozotocin (STZ; 60mg/kg) was injected intraperitoneally. After 8 weeks of treatment with IMOD™ (20 mg/kg/day), heart tissue samples were removed and used for measurement of miR-503 and CDC25 expression level as well as histological studies.
Results: Results of this study showed that diabetes decreased heart tissue angiogenesis which was associated with increased miR-503 and reduced CDC25 expression levels (p<0.05) and IMOD™ could reduce the expression of miR-503 and increase the expression of CDC25 (p<0.05). Moreover, IMOD™ extensively induced angiogenesis in the heart tissue of diabetic group. However, IMOD™ had no significant effect on expressions of miR-503 and CDC25, or angiogenesis in healthy rats.
Conclusion: This study showed that IMOD™ is able to increase angiogenesis in the heart tissue of diabetic rats. The angiogenic effect of IMOD™ is associated with reduction of miR-503 expression and increased expression of CDC25.

Keywords

Main Subjects

References

Abacı A, Oğuzhan A, Kahraman S, Eryol NK, Ünal Ş, Arınç H, Ergin A. 1999. Effect of Diabetes Mellitus on Formation of Coronary Collateral Vessels. Circulation, 99: 2239-2242.
Akbarzadeh A, Norouzian D, Mehrabi MR, Jamshidi S, Farhangi A, Allah Verdi A, Mofidian SMA, Lame Rad B. 2013. Induction of diabetes by streptozotocin in rats. Indian J Clin Biochem, 22: 60-64.
Alipour MR, Khamaneh AM, Yousefzadeh N, Mohammad-nejad D, GhadiriSoufi F. 2013. Upregulation of microRNA-146a was not accompanied by downregulation of pro-inflammatory markers in diabetic kidney. Mol Biol Rep, 40: 6477–6483.
Alva ML, Gray A, Mihaylova B, Leal J, Holman RR. 2015. The impact of diabetes‐related complications on healthcare costs: new results from the UKPDS. Diabetic Med, 32: 459-466.
Bajpai S, Mishra M, Kumar H, Tripathi K, Singh SK, Pandey HP, Singh RK. 2011. Effect of selenium on connexin expression, angiogenesis, and antioxidant status in diabetic wound healing. Biol Trace Elem Res, 144: 327-338.
Caporali, A, Meloni M, Völlenkle C, Bonci D, Sala-Newby GB, Addis R, Spinetti G, Losa S, Masson R, Baker AH, Agami R, Sage CL, Condorelli G, Madeddu P, Martelli F, Emanueli C. 2011. Deregulation of microRNA-503 Contributes to Diabetes Mellitus–Induced Impairment of Endothelial Function and Reparative Angiogenesis After Limb Ischemia. Circulation, 123: 282-291.
Carmeliet P. 2005. Angiogenesis in life, disease and medicine. Nature, 438: 932-936
Chang TC, Mendell JT. 2007. microRNAs in Vertebrate Physiology and Human Disease. Annu Rev Genomics Hum Genet, 8: 215-239.
Deepthi B, Sowjanya K, Lidiya B, Bhargavi RS, Babu PS. 2017. A Modern Review of Diabetes Mellitus: An Annihilatory Metabolic Disorder. J In Silico In Vitro Pharmacol, 3:1 .
Donzelli M, Draetta GF. 2003. Regulating mammalian checkpoints through Cdc25 inactivation. EMBO reports, 4: 641-728.
Farhoudi M, Najafi-Nesheli M, Hashemilar M, Mahmoodpoor A, Sharifipour E, Baradaran B, Taheraghdam A, Savadi-Oskouei D, Sadeghi-Bazargani H, Sadeghi-hokmabadi E, Akbari H, Rikhtegar R. 2013. Effect of IMOD™ on the inflammatory process after acute ischemic stroke: a randomized clinical trial. DARU J Pharm Sci, 21: 26.
Forbes JM, Cooper ME. 2013. Mechanisms of diabetic complications. Physiol Rev, 93: 137-188.
Furman BL. 2015. Streptozotocin‐induced diabetic models in mice and rats. Curr Protoc Pharmacol, 47: 1-20.
Heather LC, Clarke K. 2011. Metabolism, hypoxia and the diabetic heart J Mol Cell Cardiol, 50: 598-605.
Hormozi M, Talebi S, Khorram Khorshid HR, Zarnani AH, Kamali K, Jeddi-Tehrani M, Soltangoraee H, Akhondi MM. 2015. The effect of Setarud (IMODTM) on angiogenesis in transplanted human ovarian tissue to nude mice. Iran J Reproduct Med, 13: 605-614.
Huynh K, Bernardo BC, McMullen JR, Ritchie RH. 2014. Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways. Pharmacol  therapeut, 142: 375-415.
Ikeoka K, Nakaoka Y, Arita Y, Hashimoto T, Yasui T, Masaki T, Yamauchi-Takihara K, Shirai M, Komuro I, Sakata Y. 2014. Angiopoietin-1 Derived From Vascular Smooth Muscle Cells is Essential for Arteriogenesis After Hindlimb Ischemia. Circulation, 130: A15664-A15664.
Khazaei M, Salehi E. 2013. Myocardial capillary density in normal and diabetic male rats: Effect of bezafibrate. Res Pharm  Sci, 8: 119-123.
Kolluru GK, Bir SC, Kevil CG. 2012. Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing. Int J Vascul Med, Article ID 918267.
Kong W, Zhao J, He L, Cheng JQ. 2009. Strategies for Profiling MicroRNA Expression. J Cell Physiol, 218: 22-25.
Kota SK, Meher LK, Jammula S, Kota SK, Krishna S, Modi KD. 2012. Aberrant angiogenesis: The gateway to diabetic complications. India J Endocrinol Metabol, 16: 918.
Leeper NJ, Cooke JP. 2011. MicroRNA and mechanisms of impaired angiogenesis in diabetes mellitus. Circulation, 123: 236-238.
Liu H, Yu S, Zhang H, Xu J. 2012. Angiogenesis Impairment in Diabetes: Role of Methylglyoxal-Induced Receptor for Advanced Glycation Endproducts, Autophagy and Vascular Endothelial Growth Factor Receptor 2. PLOS ONE, 7: e46720.
MirzaeiBavil F, Alipour MR, Keyhanmanesh R, Alihemmati A, Ghiyasi R, Mohaddes G. 2015. Ghrelin Decreases Angiogenesis, HIF-1α and VEGF Protein Levels in Chronic Hypoxia in Lung Tissue of Male Rats. Adv Pharm Bull, 5: 315-320.
Modak M, Dixit P, Londhe J, Ghaskadbi S, Devasagayam TPA. 2007. Indian herbs and herbal drugs for the treatment of diabetes. J Clin Biochem Nutr, 40: 163-173.
Mohammadirad A, Khorram-Khorshid HR, Gharibdoost F, Abdollahi M. 2011. Setarud (IMODTM) as a Multiherbal Drug with Promising Benefits in Animal and Human Studies: A Comprehensive Review of Biochemical and Cellular Evidences. J Animal Veter Advances, 6: 1185-1192.
Mohseni-Salehi-Monfared SS, Habibollahzadeh E, Sadeghi H, Baeeri M, Abdollahi M. 2010. Efficacy of Setarud (IMOD™), a novel electromagnetically-treated multi-herbal compound, in mouse immunogenic type-1 diabetes. Arch Med Sci, 6: 663-669.
Paydary K, Emamzadeh-Fard S, Khorram Khorshid HR, Kamali K, SeyedAlinaghi SA, Mohraz M. 2012. Safety and efficacy of Setarud (IMOD TM) among people living with HIV/AIDS: a review. Recent Patents on Anti-Infective Drug Discovery, 7: 66-72.
Rippe C, Blimline M, Magerko KA, Lawson BR, LaRocca TJ, Donato AJ, Seals D R. 2012. MicroRNA changes in human arterial endothelial cells with senescence: relation to apoptosis, eNOS and inflammation. Exp gerontol, 47: 45-51.
Sarkar S, Dey BK, Dutta A. 2010. MiR-322/424 and -503 Are Induced during Muscle Differentiation and Promote Cell Cycle Quiescence and Differentiation by Down-Regulation of Cdc25A. Mol Biol Cell, 21: 2138-2149.
Shibuya M. 2011. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes  Cancer, 2: 1097-1105.
Tabatabaei-Malazy O, Larijani B, Abdollahi M. 2013. A novel management of diabetes by means of strong antioxidants’ combination. J Med Hypothes Ideas, 7: 25-30.
Tahergorabi Z, Khazaei M. 2012. Imbalance of Angiogenesis in Diabetic Complications: The Mechanisms. Int J Prevent Med, 3: 827-838.
Timofeev O, Cizmecioglu O, Settele F, Kempf T, Hoffmann I. 2012. Cdc25 Phosphatases Are Required for  Timely Assembly of CDK1-Cyclin B at the G2/M Transition. J Biol Chem, 285: 16978-16990.
Xu L, Kanasaki K, Kitada M, Koya D. 2012. Diabetic angiopathy and angiogenic defects. Fibrogenesis tissue repair, 5: 1
Yamakuchi M. 2012. MicroRNAs in Vascular Biology. Int J Vasc Med, Article ID 794898.
Avicenna Journal of Phytomedicine
Volume 8, Issue 2
March and April 2018
Pages 152-160

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