Document Type : Original Article
Authors
Abstract
Background and Aim: Cardiac rehabilitation is a new approach in various ways to increase performance and efficiency of patient. This study examined the effect of 12 weeks of endurance training with testosterone injections on Chemerin and Apelin levels in the process of rehabilitation in male adult rats with ischemic heart disease. Materials and Methods: 40 Wistar male rats (average weight 200 ± 10 g and 8 weeks old) were randomly divided into four groups (n=10) and stored in a controlled environment : 1) control group (C), 2) injection of testosterone propionate group ( TP), 3) endurance training group (ET) and 4) Endurance Training with injections of testosterone Propionate (ETTP) . Endurance training group exercised for 12 weeks (5 days/week) and testosterone propionate group were given Testosterone propionate injections (3 times/week). Isoproterenol (50 mg/kg) was dissolved in normal saline and was injected intraperitoneally (i.p.) during two days within 24 hours in order to create empirical myocardial infarction. After 12 weeks, rats anesthetized with sodium thiopental (50 mg/kg) and blood samples were taken and chemerin and apelin levels were measured by using ELISA method and data analysis was done using one-way ANOVA and post-hoc LSD tests. Results: The results revealed a significant reduction in the amount Chemerin in endurance training (p=0.008), injected testosterone (p=0.03) and endurance training with testosterone injections (p=0.01) knows shown and the significant increase significant amounts of apelin in endurance training (p=0.001), injected testosterone (p=0.001) and endurance training with testosterone injections (p=0.001) was observed. Conclusion: This study shows that injection of testosterone and endurance training in the process of rehabilitation is feasible and can have a positive effect on cardiovascular health.
Keywords
Becker, M., Rabe, k., Lebherz, C., Zugwurst, J., Goke, B., Parhofer, K.G., Lehrke, M., & Broedl, U.C. (2010). Expression of human chemerin induces insulin resistance in the skeletal muscle but does not affect weight, lipid levels, and atherosclerosis in LDL receptor knockout mice on high-fat diet. Diabetes, 59(11), 2898–2903.
Berry, M.F., Pirolli, T.J., Jayasankar, V., Burdick, J., Morine, K.J., Gardner, T.J., & Woo, Y.J. (2004). Apelin has in vivo inotropic effects on normal and failing hearts. Circulation, 110(11), 187–93.
Bozaoglu, K., Bolton, K., McMillan, J., Zimmet, p., Jowett, J., Collier, G., Walder, K., & Segal, D. (2007). Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology, 148(10), 4687–4694.
Chakaroun, R., Raschpichler, M., Kloting, N., Oberbach, A., Fleming, G., Kem, M., Schon, M.R., Shang, E., Lohmann, L., Drebler, M., Fasshauer, M., Stumvoll, M., & Bluher, M. (2012). Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism, 61(5), 706–714.
Chandrasekaran, B., Dar, O., & McDonagh, T. (2008). The role of apelin in cardiovascular function and heart failure. European Journal of Heart Failure, 10(8), 725–732.
Chang, L., Ren, Y., Liu, X., Li, W.G., Yang, J., Geng, B., Weintraub, N., & Tang, C. (2004). Protective effects of ghrelin on ischemia/reperfusion injury in the isolated rat heart. Journal Cardiovascular Pharmacology, 43(2), 165–70.
Chen, Y., Fu, L., Han, Y., Teng, Y., Sun, J., Xie, R., & Cao, J. (2012). Testosterone replacement therapy promotes angiogenesis after acute myocardial infarction by enhancing expression of cytokines HIF-1a, SDF-1a and VEGF. European Journal of Pharmacology, 684(1-3), 116–124.
Ernst, M.C., Issa, M., Goralski, K.B., & Sinal, C.J. (2010). Chemerin exacerbates glucose intolerance in mouse models of obesity and diabetes. Endocrinology, 151(5), 1998–2007.
Ernst, M.C., & Sinal, C.J. (2010). Chemerin: at the crossroads of inflammation and obesity. Trends in Endocrinology & Metabolism, 21(11), 660–667.
Flores, L.J., Figueroa, D., Sanches, I.C., Jorge, L., Irigoyen, M.C., Rodrigues, B., & De Angelis, K. (2010). Effects of exercise training on autonomic dysfunction management in an experimental model of menopause and myocardial infarction. Menopause, 17(4), 712–717.
Grover, J.K., Vats, V., Srinivas, M., Das, S.N., Jha, P., Gupta, D.K., & Mitra, D.K. (2001). Effect of metronidazole on spermatogenesis and FSH, LH and testosterone levels of pre-pubertal rats. Indian Journal Experience Biology, 39(11), 1160–1162.
Hashimoto, T., Kihara, M., Imai, N., Yoshida, S., Shimoyamada, H., Yasuzaki, H., Ishida, J., Toya, Y., Kiuchi, Y., Hirawa, N., Tamura, K., Yazawa, T., Kitamura, H., Fukamizu, A., & Umemura, S. (2007). Requirement of apelin-apelin receptor system for oxidative stress-linked atherosclerosis. American Journal Pathology, 171(5), 1705-1712.
Heinonen, M.V., Purhonen, A.K., Miettinen, P., Paakkonen M., Pirinen, E., Alhava, E., Akerman, K., Herzig, K.H. (2005). Apelin, orexin-A and leptin plasma levels in morbid obesity and effect of gastric banding. Regulatory Peptide, 130(1-2), 7-13.
Ishida, J., Hashimoto, T., Hashimoto, Y., Nishiwaki, S., Iguchi, T., Harada, S., Sugaya, T., Matsuzaki, H., Yamamoto, R., Shiota, N., Okunishi, H., Kihara, M., Umemura, S., Sugiyama, F., Yagami, K.I., Kasuya, Y., Mochizuki, N., & Fukamizu, A. (2004). Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo. Journal Biology Chemistry, 279(25), 26274–9.
Berry, M.F., Pirolli, T.J., Jayasankar, V., Burdick, J., Morine, K.J., Gardner, T.J., & Woo, Y.J. (2004). Apelin has in vivo inotropic effects on normal and failing hearts. Circulation, 110(11), 187–93.
Bozaoglu, K., Bolton, K., McMillan, J., Zimmet, p., Jowett, J., Collier, G., Walder, K., & Segal, D. (2007). Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology, 148(10), 4687–4694.
Chakaroun, R., Raschpichler, M., Kloting, N., Oberbach, A., Fleming, G., Kem, M., Schon, M.R., Shang, E., Lohmann, L., Drebler, M., Fasshauer, M., Stumvoll, M., & Bluher, M. (2012). Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism, 61(5), 706–714.
Chandrasekaran, B., Dar, O., & McDonagh, T. (2008). The role of apelin in cardiovascular function and heart failure. European Journal of Heart Failure, 10(8), 725–732.
Chang, L., Ren, Y., Liu, X., Li, W.G., Yang, J., Geng, B., Weintraub, N., & Tang, C. (2004). Protective effects of ghrelin on ischemia/reperfusion injury in the isolated rat heart. Journal Cardiovascular Pharmacology, 43(2), 165–70.
Chen, Y., Fu, L., Han, Y., Teng, Y., Sun, J., Xie, R., & Cao, J. (2012). Testosterone replacement therapy promotes angiogenesis after acute myocardial infarction by enhancing expression of cytokines HIF-1a, SDF-1a and VEGF. European Journal of Pharmacology, 684(1-3), 116–124.
Ernst, M.C., Issa, M., Goralski, K.B., & Sinal, C.J. (2010). Chemerin exacerbates glucose intolerance in mouse models of obesity and diabetes. Endocrinology, 151(5), 1998–2007.
Ernst, M.C., & Sinal, C.J. (2010). Chemerin: at the crossroads of inflammation and obesity. Trends in Endocrinology & Metabolism, 21(11), 660–667.
Flores, L.J., Figueroa, D., Sanches, I.C., Jorge, L., Irigoyen, M.C., Rodrigues, B., & De Angelis, K. (2010). Effects of exercise training on autonomic dysfunction management in an experimental model of menopause and myocardial infarction. Menopause, 17(4), 712–717.
Grover, J.K., Vats, V., Srinivas, M., Das, S.N., Jha, P., Gupta, D.K., & Mitra, D.K. (2001). Effect of metronidazole on spermatogenesis and FSH, LH and testosterone levels of pre-pubertal rats. Indian Journal Experience Biology, 39(11), 1160–1162.
Hashimoto, T., Kihara, M., Imai, N., Yoshida, S., Shimoyamada, H., Yasuzaki, H., Ishida, J., Toya, Y., Kiuchi, Y., Hirawa, N., Tamura, K., Yazawa, T., Kitamura, H., Fukamizu, A., & Umemura, S. (2007). Requirement of apelin-apelin receptor system for oxidative stress-linked atherosclerosis. American Journal Pathology, 171(5), 1705-1712.
Heinonen, M.V., Purhonen, A.K., Miettinen, P., Paakkonen M., Pirinen, E., Alhava, E., Akerman, K., Herzig, K.H. (2005). Apelin, orexin-A and leptin plasma levels in morbid obesity and effect of gastric banding. Regulatory Peptide, 130(1-2), 7-13.
Ishida, J., Hashimoto, T., Hashimoto, Y., Nishiwaki, S., Iguchi, T., Harada, S., Sugaya, T., Matsuzaki, H., Yamamoto, R., Shiota, N., Okunishi, H., Kihara, M., Umemura, S., Sugiyama, F., Yagami, K.I., Kasuya, Y., Mochizuki, N., & Fukamizu, A. (2004). Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo. Journal Biology Chemistry, 279(25), 26274–9.
James, M.F., Robert, M.K., & Andrew C.P. (2004). Comparison of tamoxifen and testosterone propionate in male rats: differential prevention of orchidectomy effects on sex organs, bone mass, growth, and the growth hormone–IGF-I axis. Journal of Andrology, 25(4), 523-34.
Joukar, S., Bashiri, H., Dabiri, S., Ghotbi, P., Sarveazad, A., Divsalar, K., Joukar, F., & Abbaszadeh, M. (2012). Cardiovascular effects of black tea and nicotine alone or in combination against experimental induced heart injury. Journal Physiology Biochemistry, 68(2), 271–279.
Kalea, A.Z., & Batlle, D. (2010). Apelin and ACE2 in cardiovascular disease. Current Opinion Investigation Drugs, 11(3), 273-82.
Keim, N., Stern, J., & Havel, P. (1998). Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women. American Journal, 68(4), 794-801.
Kontoleon, P.E., Anastasiou-Nana, M.I., Papapetrou, P.D., Alexopoulos G., Ktenas, V., Rapti, A.C., Tsagalou, E.P., & Nanas, J.N. (2003). Hormonal profile in patients with congestive heart failure. International Journal Cardiology, 87(3), 179-83.
Lina E.A., Irum Z.J., Kenneth F., Waters D.L., Villareal, D.T., & Armamento-Villareal, R. (2014). Testosterone and adipokines are determinants of physical performance, strength, and aerobic fitness in frail, obese, older adults. International Journal of Endocrinology, 2014(2014), 6.
Malkin, C.J., Pugh, P.J., West, J.N., Van Beek E.J., Jones, T.H., & Channer, K.S. (2006). Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. European Heart Journal, 27(1), 57-64.
Malkin, C.J., Pugh, P.J., Jones, R.D., Kapoor D., Channer, K.S., & Jones, T.H. (2004). The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. Journal Clinical Endocrinology Metabolism, 89(7), 3313-8.
Mirdamadi, A., Garakyaraghi, M., Pourmoghaddas, A., Bahmani, A., Mahmoudi, H., & Gharipour, M. (2014). Beneficial Effects of Testosterone Therapy on Functional Capacity, Cardiovascular Parameters, and Quality of Life in Patients with Congestive Heart Failure. BioMed Research International, 2014(2014), 7.
Pugh, P.J., Jones, T.H., & Channer, K.S. (2003). Acute hemodynamic effects of testosterone in men with chronic heart failure. Europian Heart Journal, 24(10), 909-15.
Rubinow, K.B., Snyder, C.N., Amory, J.K., Hoofnagle A.N., & Page, S.T. (2012). Acute testosterone deprivation reduced insulin sensitivity in men. Clin Endocrinol (Oxf), 76(2), 281–288.
Saremi, A., Mosleh Abadi, M.F., & Parastesh, M. (2011). Effects of twelve-week strength training on serum chemerin, TNF-α and CRP level in subjects with the metabolic syndrome. International Journal of Endocrinology Metabolism, 12(5), 536-43.
Scott, I.C., Masri, B., D'Amico, L.A., Jin, S.W., Junghblut, B., Wehman, A.M., Barier, H., Audigier, Y., & Y.R.Stainier, D. (2007). The g protein-coupled receptor agtrl1b regulates early development of myocardial progenitors. Developmental cell, 12(3), 403-413.
Stejskal, D., Karpisek, M., Hanulova, Z., & Svestak, M. (2008). Chemerin is an independent marker of the metabolic syndrome in a Caucasian population-a pilot study. Biomedical papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia, 152(2), 217-21.
Sunduz, O., zlem, A., Sumeyra, N., Mert, K., & Yuksel, H. (2014). Apelin levels in relation with hormonal and metabolic profile in patients with polycystic ovary syndrome. European Journal of Obstetrics & Gynecology and Reproductive Biology, 176(4), 168–172.
Takahashi, M., Takahashi, Y., Takahashi, K., Zolotaryov, F.N., Hong, K.S., Kitazawa, R., Lida, K., Okimura, Y., Kaji, H., Kitazawa, S., Kasuqa, M., & Chihara, K. (2008). Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3–L1 adiposities. FEBS Letter, 582(5), 573–578.
Joukar, S., Bashiri, H., Dabiri, S., Ghotbi, P., Sarveazad, A., Divsalar, K., Joukar, F., & Abbaszadeh, M. (2012). Cardiovascular effects of black tea and nicotine alone or in combination against experimental induced heart injury. Journal Physiology Biochemistry, 68(2), 271–279.
Kalea, A.Z., & Batlle, D. (2010). Apelin and ACE2 in cardiovascular disease. Current Opinion Investigation Drugs, 11(3), 273-82.
Keim, N., Stern, J., & Havel, P. (1998). Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women. American Journal, 68(4), 794-801.
Kontoleon, P.E., Anastasiou-Nana, M.I., Papapetrou, P.D., Alexopoulos G., Ktenas, V., Rapti, A.C., Tsagalou, E.P., & Nanas, J.N. (2003). Hormonal profile in patients with congestive heart failure. International Journal Cardiology, 87(3), 179-83.
Lina E.A., Irum Z.J., Kenneth F., Waters D.L., Villareal, D.T., & Armamento-Villareal, R. (2014). Testosterone and adipokines are determinants of physical performance, strength, and aerobic fitness in frail, obese, older adults. International Journal of Endocrinology, 2014(2014), 6.
Malkin, C.J., Pugh, P.J., West, J.N., Van Beek E.J., Jones, T.H., & Channer, K.S. (2006). Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. European Heart Journal, 27(1), 57-64.
Malkin, C.J., Pugh, P.J., Jones, R.D., Kapoor D., Channer, K.S., & Jones, T.H. (2004). The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. Journal Clinical Endocrinology Metabolism, 89(7), 3313-8.
Mirdamadi, A., Garakyaraghi, M., Pourmoghaddas, A., Bahmani, A., Mahmoudi, H., & Gharipour, M. (2014). Beneficial Effects of Testosterone Therapy on Functional Capacity, Cardiovascular Parameters, and Quality of Life in Patients with Congestive Heart Failure. BioMed Research International, 2014(2014), 7.
Pugh, P.J., Jones, T.H., & Channer, K.S. (2003). Acute hemodynamic effects of testosterone in men with chronic heart failure. Europian Heart Journal, 24(10), 909-15.
Rubinow, K.B., Snyder, C.N., Amory, J.K., Hoofnagle A.N., & Page, S.T. (2012). Acute testosterone deprivation reduced insulin sensitivity in men. Clin Endocrinol (Oxf), 76(2), 281–288.
Saremi, A., Mosleh Abadi, M.F., & Parastesh, M. (2011). Effects of twelve-week strength training on serum chemerin, TNF-α and CRP level in subjects with the metabolic syndrome. International Journal of Endocrinology Metabolism, 12(5), 536-43.
Scott, I.C., Masri, B., D'Amico, L.A., Jin, S.W., Junghblut, B., Wehman, A.M., Barier, H., Audigier, Y., & Y.R.Stainier, D. (2007). The g protein-coupled receptor agtrl1b regulates early development of myocardial progenitors. Developmental cell, 12(3), 403-413.
Stejskal, D., Karpisek, M., Hanulova, Z., & Svestak, M. (2008). Chemerin is an independent marker of the metabolic syndrome in a Caucasian population-a pilot study. Biomedical papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia, 152(2), 217-21.
Sunduz, O., zlem, A., Sumeyra, N., Mert, K., & Yuksel, H. (2014). Apelin levels in relation with hormonal and metabolic profile in patients with polycystic ovary syndrome. European Journal of Obstetrics & Gynecology and Reproductive Biology, 176(4), 168–172.
Takahashi, M., Takahashi, Y., Takahashi, K., Zolotaryov, F.N., Hong, K.S., Kitazawa, R., Lida, K., Okimura, Y., Kaji, H., Kitazawa, S., Kasuqa, M., & Chihara, K. (2008). Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3–L1 adiposities. FEBS Letter, 582(5), 573–578.
Tan, B.K., Chen, J., Farhatullah, S., Adya, R., Kaur, J., Heutling, D., Lewandowski, K.C., O’Hare, J.P., Lehnert, H., & Randeva, H.S. (2009). Insulin and metformin regulate circulating and adipose tissue chemerin. Diabetes, 58(9), 1971–7.
Tappler, B., & Katz, M. (1979). Pituitary-gonadal dysfunction in low-output cardiac failure. Clin Endocrinoly, 10(3), 219-26.
Taylor, R.S., Brown, A., Ebrahim, S., Jolliffe, J., Noorani, H., Rees, K., Skidmore, B., Stone, J.A., Thompson, D.R., & Oldridge, N. (2004). Exercise-Based Rehabilitation for Patients With coronary Heart Disease: Systematic review And Meta-Analysis of Randomized Controlled Trials. American Medical, 116(10), 682-692.
Venojarvi, M., Wasenius, N., Manderoos, S., Heinonen, O.J., Hernelahti, M., Lindholm, H., Surakka, J., Lindstrom, J., Aunola, S., Atalay, M., & Eriksson, J.G. (2013). Nordic walking decreased circulating chemerin and leptin concentrations in middle-aged men with impaired glucose regulation. Annals of Medicine, 45(2), 162-70.
Vigen, R., O'Donnell, C.I., Barón, A.E., Grunwald, G.K., Maddox, T.M., Bradley, S.M., Barqawi, A., Woning, G., Wierman, M.E., Plomondon, M.E., Rumsfeld, J.S., & Ho, P.M. (2014). Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. The Journal of the American Medical Association, 311(9), 967.
Wittamer, V., Franssen, J.D., Vulcano, M., Mirjolet, J.F., Le poul, E., Migeotte, I., Brezillon, S., Tyldesley, R., Blanpain, C., Detheux, M., Mantovani, A., Sozzani, S., Vassert, G., Parmentier, M., & Communi, D. (2003). Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. The Journal of Experimental Medicine, 198(7), 977-85.
Xiang Jun, Z., Li Ke, Z., Hong Xia, W., Ling Qiao, L., Li Quan, M., & Chao Shu, T. (2009). Apelin protects heart against ischemia/reperfusion injury in rat. Peptides, 30(6), 1144–1152.
Yan, Q., Zhang, Y., Hong, J., Gune, W., & Dai, M. (2011). The association of serum chemerin level with risk of coronary artery disease in Chinese adults. Journal on Endocrine, 16(2), 28-30.
Zhang, J., Ren, C.X., Qi, Y.F., Lou, L.X., Chen, L., Zhang, L.K., Wang, X., & Tang, C. (2006). Exercise training promotes expression of apelin and APJ of cardiovascular tissues in spontaneously hypertensive rats. Life Sciences, 79(12), 1153–1159.
Tappler, B., & Katz, M. (1979). Pituitary-gonadal dysfunction in low-output cardiac failure. Clin Endocrinoly, 10(3), 219-26.
Taylor, R.S., Brown, A., Ebrahim, S., Jolliffe, J., Noorani, H., Rees, K., Skidmore, B., Stone, J.A., Thompson, D.R., & Oldridge, N. (2004). Exercise-Based Rehabilitation for Patients With coronary Heart Disease: Systematic review And Meta-Analysis of Randomized Controlled Trials. American Medical, 116(10), 682-692.
Venojarvi, M., Wasenius, N., Manderoos, S., Heinonen, O.J., Hernelahti, M., Lindholm, H., Surakka, J., Lindstrom, J., Aunola, S., Atalay, M., & Eriksson, J.G. (2013). Nordic walking decreased circulating chemerin and leptin concentrations in middle-aged men with impaired glucose regulation. Annals of Medicine, 45(2), 162-70.
Vigen, R., O'Donnell, C.I., Barón, A.E., Grunwald, G.K., Maddox, T.M., Bradley, S.M., Barqawi, A., Woning, G., Wierman, M.E., Plomondon, M.E., Rumsfeld, J.S., & Ho, P.M. (2014). Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. The Journal of the American Medical Association, 311(9), 967.
Wittamer, V., Franssen, J.D., Vulcano, M., Mirjolet, J.F., Le poul, E., Migeotte, I., Brezillon, S., Tyldesley, R., Blanpain, C., Detheux, M., Mantovani, A., Sozzani, S., Vassert, G., Parmentier, M., & Communi, D. (2003). Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. The Journal of Experimental Medicine, 198(7), 977-85.
Xiang Jun, Z., Li Ke, Z., Hong Xia, W., Ling Qiao, L., Li Quan, M., & Chao Shu, T. (2009). Apelin protects heart against ischemia/reperfusion injury in rat. Peptides, 30(6), 1144–1152.
Yan, Q., Zhang, Y., Hong, J., Gune, W., & Dai, M. (2011). The association of serum chemerin level with risk of coronary artery disease in Chinese adults. Journal on Endocrine, 16(2), 28-30.
Zhang, J., Ren, C.X., Qi, Y.F., Lou, L.X., Chen, L., Zhang, L.K., Wang, X., & Tang, C. (2006). Exercise training promotes expression of apelin and APJ of cardiovascular tissues in spontaneously hypertensive rats. Life Sciences, 79(12), 1153–1159.
)