Anatomy and Cell Biology

Korean Association of Anatomists (대한해부학회)
권호 표지
DOI QR코드

DOI QR Code

Histomorphological changes in the common carotid artery of the male rat in induced hypogonadism

  • Cheruiyot, Isaac (Department of Human Anatomy, University of Nairobi) ;
  • Olabu, Beda (Department of Human Anatomy, University of Nairobi) ;
  • Kamau, Martin (Department of Human Anatomy, University of Nairobi) ;
  • Ongeti, Kevin (Department of Human Anatomy, University of Nairobi) ;
  • Mandela, Pamela (Department of Human Anatomy, University of Nairobi)
  • Received : 2018.04.30
  • Accepted : 2018.07.03
  • Published : 2018.12.30
⟨ Previous Next ⟩

Abstract

The role of androgens in the development of cardiovascular diseases remains controversial. The current study therefore sought to determine the changes in the histomorphology of the common carotid artery of the male rat in orchidectomy-induced hypogonadism. Twenty-two Rattus norvegicus male rats aged 2 months were used. The rats were randomly assigned into baseline (n=4), experimental (n=9), and control (n=9) groups. Hypogonadism was surgically induced in the experimental group by bilateral orchiectomy under local anesthesia. At experiment weeks 3, 6, and 9, three rats from each group (experimental and control) were euthanized, their common carotid artery harvested, and routine processing was done for paraffin embedding, sectioning, and staining. The photomicrographs were taken using a digital photomicroscope for morphometric analysis. Orchidectomy resulted in the development of vascular fibrosis, with a significant increase in collagen fiber density and decrease in smooth muscle and elastic fiber density. Moreover, there was development of intimal hyperplasia, with fragmentation of medial elastic lamellae in the common carotid artery of the castrated rats. Orchidectomy induces adverse changes in structure of the common carotid artery of the male rat. These changes may impair vascular function, therefore constituting a possible structural basis for the higher incidences of cardiovascular diseases observed in hypogonadism.

Keywords

References

  1. McGrath KC, McRobb LS, Heather AK. Androgen therapy and atherosclerotic cardiovascular disease. Vasc Health Risk Manag 2008;4:11-21. https://doi.org/10.2147/VHRM.S1255
  2. Maravelias C, Dona A, Stefanidou M, Spiliopoulou C. Adverse effects of anabolic steroids in athletes: a constant threat. Toxicol Lett 2005;158:167-75. https://doi.org/10.1016/j.toxlet.2005.06.005
  3. Haring R, Baumeister SE, Volzke H, Dorr M, Felix SB, Kroemer HK, Nauck M, Wallaschofski H. Prospective association of low total testosterone concentrations with an adverse lipid profile and increased incident dyslipidemia. Eur J Cardiovasc Prev Rehabil 2011;18:86-96. https://doi.org/10.1097/HJR.0b013e32833c1a8d
  4. Fahed AC, Gholmieh JM, Azar ST. Connecting the lines between hypogonadism and atherosclerosis. Int J Endocrinol 2012;2012:793953.
  5. Yeap BB, Hyde Z, Almeida OP, Norman PE, Chubb SA, Jamrozik K, Flicker L, Hankey GJ. Lower testosterone levels predict incident stroke and transient ischemic attack in older men. J Clin Endocrinol Metab 2009;94:2353-9. https://doi.org/10.1210/jc.2008-2416
  6. Martin-Merino E, Johansson S, Morris T, Garcia Rodriguez LA. Androgen deprivation therapy and the risk of coronary heart disease and heart failure in patients with prostate cancer: a nested case-control study in UK primary care. Drug Saf 2011;34:1061-77. https://doi.org/10.2165/11594540-000000000-00000
  7. Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A, Day N. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation 2007;116:2694-701. https://doi.org/10.1161/CIRCULATIONAHA.107.719005
  8. Menke A, Guallar E, Rohrmann S, Nelson WG, Rifai N, Kanarek N, Feinleib M, Michos ED, Dobs A, Platz EA. Sex steroid hormone concentrations and risk of death in US men. Am J Epidemiol 2010;171:583-92. https://doi.org/10.1093/aje/kwp415
  9. Karakitsos D, Patrianakos AP, De Groot E, Boletis J, Karabinis A, Kyriazis J, Samonis G, Parthenakis FI, Vardas PE, Daphnis E. Androgen deficiency and endothelial dysfunction in men with end-stage kidney disease receiving maintenance hemodialysis. Am J Nephrol 2006;26:536-43. https://doi.org/10.1159/000097816
  10. Kumar N, Swamy R, Patil J, Guru A, Aithal A, Shetty P. Presence of arteriovenous communication between left testicular vessels and its clinical significance. Case Rep Vasc Med 2014;2014:160824.
  11. Christe N, Meier CA. Hypotestosteronaemia in the aging male: should we treat it? Swiss Med Wkly 2015;145:w14216.
  12. Alexandersen P, Haarbo J, Byrjalsen I, Lawaetz H, Christiansen C. Natural androgens inhibit male atherosclerosis: a study in castrated, cholesterol-fed rabbits. Circ Res 1999;84:813-9. https://doi.org/10.1161/01.RES.84.7.813
  13. Muraleedharan V, Jones TH. Testosterone and the metabolic syndrome. Ther Adv Endocrinol Metab 2010;1:207-23. https://doi.org/10.1177/2042018810390258
  14. Bobjer J, Naumovska M, Giwercman YL, Giwercman A. High prevalence of androgen deficiency and abnormal lipid profile in infertile men with non-obstructive azoospermia. Int J Androl 2012;35:688-94. https://doi.org/10.1111/j.1365-2605.2012.01277.x
  15. Castela A, Vendeira P, Costa C. Testosterone, endothelial health, and erectile function. ISRN Endocrinol 2011;2011:839149.
  16. Hanke H, Lenz C, Hess B, Spindler KD, Weidemann W. Effect of testosterone on plaque development and androgen receptor expression in the arterial vessel wall. Circulation 2001;103:1382-5. https://doi.org/10.1161/01.CIR.103.10.1382
  17. Chan YX, Knuiman MW, Hung J, Divitini ML, Handelsman DJ, Beilby JP, McQuillan B, Yeap BB. Testosterone, dihydrotestosterone and estradiol are differentially associated with carotid intima-media thickness and the presence of carotid plaque in men with and without coronary artery disease. Endocr J 2015;62:777-86. https://doi.org/10.1507/endocrj.EJ15-0196
  18. Farias JM, Tinetti M, Khoury M, Umpierrez GE. Low testosterone concentration and atherosclerotic disease markers in male patients with type 2 diabetes. J Clin Endocrinol Metab 2014;99:4698-703. https://doi.org/10.1210/jc.2014-2585
  19. Gilliver SC, Ashworth JJ, Mills SJ, Hardman MJ, Ashcroft GS. Androgens modulate the inflammatory response during acute wound healing. J Cell Sci 2006;119(Pt 4):722-32. https://doi.org/10.1242/jcs.02786
  20. Pelletier G, Lihrmann I, Dubessy C, Luu-The V, Vaudry H, Labrie F. Androgenic down-regulation of urotensin II precursor, urotensin II-related peptide precursor and androgen receptor mRNA in the mouse spinal cord. Neuroscience 2005;132:689-96. https://doi.org/10.1016/j.neuroscience.2004.12.045
  21. Rodriguez-Moyano M, Diaz I, Dionisio N, Zhang X, Avila- Medina J, Calderon-Sanchez E, Trebak M, Rosado JA, Ordonez A, Smani T. Urotensin-II promotes vascular smooth muscle cell proliferation through store-operated calcium entry and EGFR transactivation. Cardiovasc Res 2013;100:297-306. https://doi.org/10.1093/cvr/cvt196
  22. Zhao J, Zhang SF, Shi Y, Ren LQ. Effects of urotensin II and its specific receptor antagonist urantide on rat vascular smooth muscle cells. Bosn J Basic Med Sci 2013;13:78-83. https://doi.org/10.17305/bjbms.2013.2369
  23. Morgentaler A. Testosterone deficiency and cardiovascular mortality. Asian J Androl 2015;17:26-31. https://doi.org/10.4103/1008-682X.143248
  24. Traish A, Kim N. The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function. J Sex Med 2005;2:759-70. https://doi.org/10.1111/j.1743-6109.2005.00094.x
  25. Olabu BO. Structural changes in the rabbit penile architecture in induced hypogonadism [thesis]. Nairobi: University of Nairobi; 2014.
  26. Sanchez-Mas J, Turpin MC, Lax A, Ruiperez JA, Valdes Chavarri M, Pascual-Figal DA. Differential actions of eplerenone and spironolactone on the protective effect of testosterone against cardiomyocyte apoptosis in vitro. Rev Esp Cardiol 2010;63:779-87. https://doi.org/10.1016/S0300-8932(10)70180-9
  27. Kang NN, Fu L, Xu J, Han Y, Cao JX, Sun JF, Zheng M. Testosterone improves cardiac function and alters angiotensin II receptors in isoproterenol-induced heart failure. Arch Cardiovasc Dis 2012;105:68-76. https://doi.org/10.1016/j.acvd.2011.12.002
  28. Traish AM, Goldstein I, Kim NN. Testosterone and erectile function: from basic research to a new clinical paradigm for managing men with androgen insufficiency and erectile dysfunction. Eur Urol 2007;52:54-70. https://doi.org/10.1016/j.eururo.2007.02.034
  29. Ikeda Y, Aihara K, Yoshida S, Sato T, Yagi S, Iwase T, Sumitomo Y, Ise T, Ishikawa K, Azuma H, Akaike M, Kato S, Matsumoto T. Androgen-androgen receptor system protects against angiotensin II-induced vascular remodeling. Endocrinology 2009;150:2857-64. https://doi.org/10.1210/en.2008-1254
  30. Wespes E. Smooth muscle pathology and erectile dysfunction. Int J Impot Res 2002;14 Suppl 1:S17-21. https://doi.org/10.1038/sj.ijir.3900792
  31. Traish AM, Kim N. Weapons of penile smooth muscle destruction: androgen deficiency promotes accumulation of adipocytes in the corpus cavernosum. Aging Male 2005;8:141-6. https://doi.org/10.1080/13685530500328183
  32. Dandona P, Rosenberg MT. A practical guide to male hypogonadism in the primary care setting. Int J Clin Pract 2010;64:682-96. https://doi.org/10.1111/j.1742-1241.2010.02355.x
  33. Rzucidlo EM, Martin KA, Powell RJ. Regulation of vascular smooth muscle cell differentiation. J Vasc Surg 2007;45 Suppl A:A25-32.
  34. Arnold JT, Isaacs JT. Mechanisms involved in the progression of androgen-independent prostate cancers: it is not only the cancer cell's fault. Endocr Relat Cancer 2002;9:61-73.
  35. Corradi LS, Goes RM, Carvalho HF, Taboga SR. Inhibition of 5-alpha-reductase activity induces stromal remodeling and smooth muscle de-differentiation in adult gerbil ventral prostate. Differentiation 2004;72:198-208. https://doi.org/10.1111/j.1432-0436.2004.07205004.x
  36. Lacolley P, Regnault V, Nicoletti A, Li Z, Michel JB. The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles. Cardiovasc Res 2012;95:194-204. https://doi.org/10.1093/cvr/cvs135
  37. Ailawadi G, Eliason JL, Upchurch GR Jr. Current concepts in the pathogenesis of abdominal aortic aneurysm. J Vasc Surg 2003;38:584-8. https://doi.org/10.1016/S0741-5214(03)00324-0
  38. Clarke MC, Figg N, Maguire JJ, Davenport AP, Goddard M, Littlewood TD, Bennett MR. Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nat Med 2006;12:1075-80. https://doi.org/10.1038/nm1459
  39. El-Sakka AI. Reversion of penile fibrosis: Current information and a new horizon. Arab J Urol 2011;9:49-55. https://doi.org/10.1016/j.aju.2011.03.013
  40. Chung CC, Kao YH, Chen YJ, Chen YJ. Androgen modulates cardiac fibrosis contributing to gender differences on heart failure. Aging Male 2013;16:22-7. https://doi.org/10.3109/13685538.2012.754008
  41. Culic V. Androgens in cardiac fibrosis and other cardiovascular mechanisms. Int J Cardiol 2015;179:190-2. https://doi.org/10.1016/j.ijcard.2014.11.079
  42. Ikeda Y, Aihara K, Sato T, Akaike M, Yoshizumi M, Suzaki Y, Izawa Y, Fujimura M, Hashizume S, Kato M, Yagi S, Tamaki T, Kawano H, Matsumoto T, Azuma H, Kato S, Matsumoto T. Androgen receptor gene knockout male mice exhibit impaired cardiac growth and exacerbation of angiotensin II-induced cardiac fibrosis. J Biol Chem 2005;280:29661-6. https://doi.org/10.1074/jbc.M411694200
  43. Darby IA, Hewitson TD. Fibroblast differentiation in wound healing and fibrosis. Int Rev Cytol 2007;257:143-79.
  44. Chipuk JE, Cornelius SC, Pultz NJ, Jorgensen JS, Bonham MJ, Kim SJ, Danielpour D. The androgen receptor represses transforming growth factor-beta signaling through interaction with Smad3. J Biol Chem 2002;277:1240-8. https://doi.org/10.1074/jbc.M108855200
  45. Placencio VR, Sharif-Afshar AR, Li X, Huang H, Uwamariya C, Neilson EG, Shen MM, Matusik RJ, Hayward SW, Bhowmick NA. Stromal transforming growth factor-beta signaling mediates prostatic response to androgen ablation by paracrine Wnt activity. Cancer Res 2008;68:4709-18. https://doi.org/10.1158/0008-5472.CAN-07-6289
  46. Petrov VV, Fagard RH, Lijnen PJ. Stimulation of collagen production by transforming growth factor-beta1 during differentiation of cardiac fibroblasts to myofibroblasts. Hypertension 2002;39:258-63. https://doi.org/10.1161/hy0202.103268
  47. Pohlers D, Brenmoehl J, Loffler I, Muller CK, Leipner C, Schultze-Mosgau S, Stallmach A, Kinne RW, Wolf G. TGF-beta and fibrosis in different organs: molecular pathway imprints. Biochim Biophys Acta 2009;1792:746-56. https://doi.org/10.1016/j.bbadis.2009.06.004
  48. Sorescu D. Smad3 mediates angiotensin II- and TGF-beta1-induced vascular fibrosis: Smad3 thickens the plot. Circ Res 2006;98:988-9. https://doi.org/10.1161/01.RES.0000221824.87718.c0
  49. Chow MJ, Turcotte R, Lin CP, Zhang Y. Arterial extracellular matrix: a mechanobiological study of the contributions and interactions of elastin and collagen. Biophys J 2014;106:2684-92. https://doi.org/10.1016/j.bpj.2014.05.014
  50. Shao JS, Sierra OL, Cohen R, Mecham RP, Kovacs A, Wang J, Distelhorst K, Behrmann A, Halstead LR, Towler DA. Vascular calcification and aortic fibrosis: a bifunctional role for osteopontin in diabetic arteriosclerosis. Arterioscler Thromb Vasc Biol 2011;31:1821-33. https://doi.org/10.1161/ATVBAHA.111.230011
  51. Iannaccone PM, Jacob HJ. Rats! Dis Model Mech 2009;2:206-10. https://doi.org/10.1242/dmm.002733
  52. Wagenseil JE, Mecham RP. New insights into elastic fiber assembly. Birth Defects Res C Embryo Today 2007;81:229-40. https://doi.org/10.1002/bdrc.20111
  53. Sherratt MJ. Tissue elasticity and the ageing elastic fibre. Age (Dordr) 2009;31:305-25. https://doi.org/10.1007/s11357-009-9103-6
  54. Chung AW, Au Yeung K, Sandor GG, Judge DP, Dietz HC, van Breemen C. Loss of elastic fiber integrity and reduction of vascular smooth muscle contraction resulting from the upregulated activities of matrix metalloproteinase-2 and -9 in the thoracic aortic aneurysm in Marfan syndrome. Circ Res 2007;101:512-22. https://doi.org/10.1161/CIRCRESAHA.107.157776
  55. Lau AC, Rosenberg H, Duong TT, McCrindle BW, Yeung RS. Elastolytic matrix metalloproteinases and coronary outcome in children with Kawasaki disease. Pediatr Res 2007;61:710-5. https://doi.org/10.1203/pdr.0b013e318053418b
  56. Wagenseil JE, Mecham RP. Elastin in large artery stiffness and hypertension. J Cardiovasc Transl Res 2012;5:264-73. https://doi.org/10.1007/s12265-012-9349-8
  57. Han YP, Tuan TL, Wu H, Hughes M, Garner WL. TNF-alpha stimulates activation of pro-MMP2 in human skin through NF-(kappa)B mediated induction of MT1-MMP. J Cell Sci 2001;114(Pt 1): 131-9.
  58. Gordon GM, Ledee DR, Feuer WJ, Fini ME. Cytokines and signaling pathways regulating matrix metalloproteinase-9 (MMP-9) expression in corneal epithelial cells. J Cell Physiol 2009;221:402-11. https://doi.org/10.1002/jcp.21869
  59. Traish AM, Guay AT. Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidence. J Sex Med 2006;3:382-404.
  60. Cecelja M, Chowienczyk P. Role of arterial stiffness in cardiovascular disease. JRSM Cardiovasc Dis 2012;1:cvd.2012.012016.
  61. O'Rourke MF, Hashimoto J. Mechanical factors in arterial aging: a clinical perspective. J Am Coll Cardiol 2007;50:1-13. https://doi.org/10.1016/j.jacc.2006.12.050
  62. Fleenor BS. Large elastic artery stiffness with aging: novel translational mechanisms and interventions. Aging Dis 2013;4:76-83.
  63. Jacob T, Hingorani A, Ascher E. Role of apoptosis and proteolysis in the pathogenesis of iliac artery aneurysms. Vascular 2005;13:34-42. https://doi.org/10.1258/rsmvasc.13.1.34
  64. Isenburg JC, Simionescu DT, Starcher BC, Vyavahare NR. Elastin stabilization for treatment of abdominal aortic aneurysms. Circulation 2007;115:1729-37. https://doi.org/10.1161/CIRCULATIONAHA.106.672873
  65. Oka R, Utsumi T, Endo T, Yano M, Kamijima S, Kamiya N, Shirai K, Suzuki H. Effect of androgen deprivation therapy on arterial stiffness and serum lipid profile changes in patients with prostate cancer: a prospective study of initial 6-month follow-up. Int J Clin Oncol 2016;21:389-96. https://doi.org/10.1007/s10147-015-0891-7
  66. Dockery F, Bulpitt CJ, Agarwal S, Vernon C, Rajkumar C. Effect of androgen suppression compared with androgen receptor blockade on arterial stiffness in men with prostate cancer. J Androl 2009;30:410-5. https://doi.org/10.2164/jandrol.108.006924

Cited by

  1. Relative energy deficiency in sports (RED-S): elucidation of endocrine changes affecting the health of males and females vol.20, pp.1, 2018, https://doi.org/10.1007/s42000-020-00214-w