Expression of HIF-1, VEGF-β and Caspase-3 in Myocardium of Rats Subjected to Hypoxic-Hyperglycemic Condition
DOI:
https://doi.org/10.7439/ijbr.v9i12.4968Abstract
Introduction: Studies of the protective effects of insulin on endothelial impairments are still very limited. Aim: This study is intended to find out the effect of insulin injection on expression of HIF-1, VEGF-β, and caspase-3 in myocardial tissues of rats subjected to hypoxic-hyperglycemic condition. Materials and methods: Wistar rats (n=30) were subjected to hyperglycemic by alloxan injection and be hypoxic by exposuring the animal to a normal and low oxygen tension alternatingly. The test animals then grouped into two. The first group was treated with insulin NPH, the second one was not. Results: Results showed that expression of HIF-1 and caspase-3 did not significantly affected by insulin treatments. However, expression of VEGF-β was siginificantly increased by insulit injection. Conclusion: In conclussion, insulin has pontential to be used as a ptotective agent against endothelial impairments in rats experienced hypoxia and hyperglycemia. Used for easily cloning the properly namespaced rectDownloads
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References
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Fan X., Heijnen C.J., Van der Kooij M.A., Groenendaal F. Dan van Bel F. The role and regulation of alpha hypoxia-induced factors in the brain and brain of neonatal hypoxia-ischemic. Brain Research Reviews, 2009; 62(1): 99-108.
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Lu M, Amano S, Miyamoto K, Garland R, Keough K, Qin W. and Adamis AP. Insulin-induced vascular endothelial growth factor expression in retina. Invest Ophthalmol Vis Sci., 1999; 40(13):3281-6.
Hao D., Ding ZY, Wang C, Li SQ, He H, Liang LB. Effects of VEGF on Proliferation, Apoptosis and Insulin Secretion in Rat Pancreatic Islet Cells. [Article in Chinese]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2016; 47(1):33-8.
Cai L, Li W, Wang G, Guo L, Jiang Y, Kang YJ. Hyperglycemia-induced apoptosis in mouse myocardium: mitochondrial cytochrome C-mediated caspase-3 activation pathway. Diabetes. 2002; 51(6): 1938-48.
Al-Harbi A.M. Frequency of Risk Factors for Coronary Heart Disease among Diabetic Patients in Al Rabwah PHC Center in Riyadh. J Family Community Med., 2004; 11(2): 53-58.
Ishihara M. Acute hyperglycemia in patients with acute myocardial infarction. Circ J. 2012; 76(3): 563-71.
Ferreira J.V. Diabetes, hypoxia and cardiovascular disease: From molecular mechanism to treatment. Rev. Port. Cardiol. 2017; 36(5): 375-376. DOI: 10.1016/j.repce.2017.04.008
Nyengaard J.R., Ido Y., Kilo C. and Williamson J.R. Interactions between Hyperglycemia and Hypoxia: Implications for Diabetic Retinopathy. Diabetes, 2004; 53(11): 2931-2938. DOI: https://doi.org/10.2337/diabetes.53.11.2931
Catrina SB, Okamoto K, Pereira T, Brismar K. and Poellinger L. Hyperglycemia regulate hypoxia-inducible factor-1alpha protein stability and function. Diabetes. 2004; 53(12):3226-32.
Ke Q. and Costa M. Hypoxia-Inducible Factor-1 (HIF-1). Molecular Pharmacology, 2006; 70 (5): 1469-1480; DOI: https://doi.org/10.1124/mol.106.027029
Krock, B. L., Skuli, N., & Simon, M. C. (2011). Hypoxia-Induced Angiogenesis: Good and Evil. Genes & Cancer, 2011; 2(12): 1117–1133. Doi: http://doi.org/10.1177/1947601911423654
Ramakrishnan, S., Anand, V., & Roy, S. Vascular Endothelial growth factor signaling in hypoxia and Inflammation. Journal of Neuroimmune Pharmacology 2014; 9(2): 142-160. Doi: http://doi.org/10.1007/s11481-014-9531-7.
Jin K, Mao XO, Batteur SP, McEachron E, Leahy A. and Greenberg DA. Caspase-3 and the regulation of hypoxic neuronal death by vascular endothelial growth factor. Neuroscience. 2001;108(2):351-8.
Carreras, A., Kayali, F., Zhang, J., Hirotsu, C., Wang, Y., & Gozal, D. Metabolic effects of intermittent hypoxia in mice: steady versus high-frequency applied hypoxia daily during the rest period. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2012; 303(7): R700-R709. Doi: http://doi.org/10.1152/ajpregu.00258.2012
Ramalho A.R., Toscano A., Pereira P., Girão H., Gonçalves L. and Marques C. Hyperglycemia-induced degradation of HIF-1α contributes to impaired response of cardiomyocytes to hypoxia. Rev. Port. Cardiol., 2017; 36(5):367-373. Doi: doi.org/10.1016/j.repce.2016.09.015
Ceriello A. Acute hyperglycaemia: a new risk factor during myocardial infarction. European Heart Journal, 2005; 26(4): 328–33. Doi: https://doi.org/10.1093/eurheartj/ehi049
Yu, H., Che, X., Xu, X., Zheng, M., Zhao, Y., He, W., Yu, J., Xiong, J., Li, W. Insulin protects apoptotic cardiomyocytes from hypoxia/reoxygenation injury through the sphingosine kinase/sphingosine 1-phosphate axis. PloS one, 2013; 8(12): e80644. doi:10.1371/journal.pone.0080644
Kohn D.F., Clifford C.B., 2002 - Biology and diseases of rats. In: J. G Fox, L.C. Anderson, F.M. Lowe, et al., eds. Laboratory Animal Medicine, 2nd ed. New York: Academic Press, 121-167.
Fajardo R.J, Karim L., Calley V.I. and Bouxsein M.L. A Review of Rodent Models of Type 2 Diabetic Skeletal Fragility. Journal of Bone and Mineral Research, 2014; 29(5): 1025–1040. DOI: 10.1002/jbmr.2210
Darnall, R. A., Chen, X., Nemani, K. V., Sirieix, C. M., Gimi, B., Knoblach, S., McEntire, B. L. Hunt, C. E. Early postnatal exposure to intermittent hypoxia in rodents is proinflammatory, impairs white matter integrity, and alters brain metabolism. Pediatric research, 2017; 82(1):164-172.
Xiao, H., Gu, Z., Wang, G., & Zhao, T. The possible mechanisms underlying the impairment of HIF-1α pathway signaling in hyperglycemia and the beneficial effects of certain therapies. International journal of medical sciences, 2013; 10(10):1412-21. doi:10.7150/ijms.5630
Siagian M., Lousiana M., Santoso D.I.S. and Endardjo S. Effects of anaerobic exercise and detraining on the caspase-3 expression of rat ventricular cardiomyocyte. Medical Journal of Indonesia, 2015; 24(2): 84-90. Doi: https://doi.org/10.13181/mji.v24i2.1220
Communal C., Sumandea M., de Tombe P., Narula J., Solaro R.J. and Hajjar R. J. Functional consequences of caspase activation in cardiac myocytes. PNAS 2002; 99 (9): 6252-6256.
Fan X., Heijnen C.J., Van der Kooij M.A., Groenendaal F. Dan van Bel F. The role and regulation of alpha hypoxia-induced factors in the brain and brain of neonatal hypoxia-ischemic. Brain Research Reviews, 2009; 62(1): 99-108.
Oltmanns K.M., Gehring H., Rudolf S., Schultes B., Hackenberg C., Schweiger U, Born J., Fehm H.L. and Peters A. 'Acute hypoxia decreases plasma VEGF concentration in healthy humans. American Journal of Physiology-Endocrinology and Metabolism, 2006; 290 (3): E434-9.
Lu M, Amano S, Miyamoto K, Garland R, Keough K, Qin W. and Adamis AP. Insulin-induced vascular endothelial growth factor expression in retina. Invest Ophthalmol Vis Sci., 1999; 40(13):3281-6.
Hao D., Ding ZY, Wang C, Li SQ, He H, Liang LB. Effects of VEGF on Proliferation, Apoptosis and Insulin Secretion in Rat Pancreatic Islet Cells. [Article in Chinese]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2016; 47(1):33-8.
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2018-12-30
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Expression of HIF-1, VEGF-β and Caspase-3 in Myocardium of Rats Subjected to Hypoxic-Hyperglycemic Condition. Int Jour of Biomed Res [Internet]. 2018 Dec. 30 [cited 2025 Mar. 12];9(12):403-8. Available from: https://ssjournals.co.in/index.php/ijbr/article/view/4968