Castration induces progressive increase in the carotid intima-medial thickness of the male rat

Yıl 2018, Cilt: 12 Sayı: 2, 65 - 70, 15.08.2018

İsaac Cheruiyot Beda Olabu Martin Kamau Kevin Ongeti Pamela Mandela

Öz

Objectives: The role of androgens in the development of cardiovascular diseases remains controversial. The current study

therefore aimed to determine the changes in the carotid intima-medial thickness of the male rat in surgically-induced hypogonadism.

Methods: Twenty-two Rattus norvegicus male rats aged two months were used. The rats were randomly assigned into baseline

(4), experimental (9) and control (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.

Results: The mean carotid intima-median thickness was 321.97 μm at baseline. There was a progressive increase in the carotid

intima-median thickness by 17.6%, 37% and 67.1% of the baseline values in the castrated group at the end of the third, sixth

and ninth week respectively (p<0.001). Although the carotid intima-median thickness increased in the non-castrated group with

increasing duration of the study, these increases were not statistically significant (p=0.110). The increase in carotid intima-median

thickness was associated with hyperplasia of the intimal layer as well as increased deposition of collagen fibers in the medial

layer.

Conclusion: Androgen deprivation by surgical castration induces a progressive increase in the carotid intima-median thickness.

This may constitute an anatomical basis for the higher predisposition of hypogonadal males to cardiovascular diseases.

Anahtar Kelimeler

androgens, carotid intima-medial thickness, castration, cardiovascular disease, hypogonadism

Kaynakça

• 1. Liviakis L, Pogue B, Paramsothy P, Bourne A, Gill EA. Carotid intima-media thickness for the practicing lipidologist. Journal of clinical lipidology. 2010 Jan 1;4(1):24-35.2. Kasliwal RR, Bansal M, Desai D, Sharma M. Carotid intima–media thickness: Current evidence, practices, and Indian experience. Indian journal of endocrinology and metabolism. 2014 Jan;18(1):13.3. Provost EB, Madhloum N, Panis LI, De Boever P, Nawrot TS. Carotid intima-media thickness, a marker of subclinical atherosclerosis, and particulate air pollution exposure: the meta-analytical evidence. PloS one. 2015 May 13;10(5):e0127014.4. Holland Z, Ntyintyane LM, Raal FJ, Gill GV. Carotid intima–media thickness is a predictor of coronary artery disease in South African black patients. Cardiovascular Journal of Africa. 2009; 20, 237–239.5. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation. 2007 Jan 30;115(4):459-67.6. Hurst RT, Ng DW, Kendall C, Khandheria B. Clinical use of carotid intima-media thickness: review of the literature. Journal of the American Society of Echocardiography. 2007 Jul 1;20(7):907-14.7. Peters SA, den Ruijter HM, Grobbee DE, Bots ML. Results from a carotid intima-media thickness trial as a decision tool for launching a large scale morbidity and mortality trial. Circulation: Cardiovascular Imaging. 2012 Jan 1:CIRCIMAGING-112.8. Bots ML. Carotid intima-media thickness as a surrogate marker for cardiovascular disease in intervention studies. Current medical research and opinion. 2006 Nov 1;22(11):2181-90.9. Alexandersen P, Haarbo J, Byrjalsen I, Lawaetz H, Christiansen C. Natural androgens inhibit male atherosclerosis: a study in castrated, cholesterol-fed rabbits. Circulation Research. 1999 Apr 16;84(7):813-9.10. McGrath KC, McRobb LS, Heather AK. Androgen therapy and atherosclerotic cardiovascular disease. Vascular health and risk management. 2008 Feb;4(1):11.11. Maravelias C, Dona A, Stefanidou M, Spiliopoulou C. Adverse effects of anabolic steroids in athletes: a constant threat. Toxicology letters. 2005 Sep 15;158(3):167-75.12. Luque-Ramírez M, Mendieta-Azcona C, Alvarez-Blasco F, Escobar-Morreale HF. Androgen excess is associated with the increased carotid intima-media thickness observed in young women with polycystic ovary syndrome. Human reproduction. 2007 Oct 11;22(12):3197-203.13. Allameh Z, Rouholamin S, Adibi A, Mehdipour M, Adeli M. Does carotid intima-media thickness have relationship with polycystic ovary syndrome?. International journal of preventive medicine. 2013 Nov;4(11):1266.14. Kim MS, Dao-Tran A, Davidowitz E, Tseng T, Gilsanz V, Ryabets-Lienhard A, Nguyen E, Geffner ME. Carotid intima-media thickness is associated with increased androgens in adolescents and young adults with classical congenital adrenal hyperplasia. Hormone research in paediatrics. 2016;85(4):242-9.15. Haring R, Baumeister SE, Völzke H, Dörr 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. European Journal of Cardiovascular Prevention & Rehabilitation. 2011 Feb;18(1):86-96.16. Fahed AC, Gholmieh JM, Azar ST. Connecting the lines between hypogonadism and atherosclerosis. International journal of endocrinology. 2012;2012.17. Soisson V, Brailly-Tabard S, Empana JP, Féart C, Ryan J, Bertrand M, Guiochon-Mantel A, Scarabin PY. Low plasma testosterone and elevated carotid intima-media thickness: importance of low-grade inflammation in elderly men. Atherosclerosis. 2012 Jul 1;223(1):244-9.18. Martín-Merino E, Johansson S, Morris T, Rodríguez LA. Androgen deprivation therapy and the risk of coronary heart disease and heart failure in patients with prostate cancer. Drug safety. 2011 Nov 1;34(11):1061-77.19. 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 Dec 4;116(23):2694-701.20. 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. American journal of epidemiology. 2010 Jan 18;171(5):583-92.21. 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. American journal of nephrology. 2006;26(6):536-43.22. 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 reports in vascular medicine. 2014;2014.23. Christe N, Meier CA. Hypotestosteronaemia in the aging male: should we treat it. Swiss Med Wkly. 2015 Nov 24;145:w14216.24. Muller M, van den Beld AW, Bots ML, Grobbee DE, Lamberts SW, van der Schouw YT. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation. 2004 May 4;109(17):2074-9.25. Farias JM, Tinetti M, Khoury M, Umpierrez GE. Low testosterone concentration and atherosclerotic disease markers in male patients with type 2 diabetes. The Journal of Clinical Endocrinology & Metabolism. 2014 Dec 1;99(12):4698-703.26. 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. Endocrine journal. 2015;62(9):777-86.27. Gilliver SC, Ashworth JJ, Mills SJ, Hardman MJ, Ashcroft GS. Androgens modulate the inflammatory response during acute wound healing. Journal of cell science. 2006 Feb 15;119(4):722-32.28. Shiota M, Song Y, Takeuchi A, Yokomizo A, Kashiwagi E, Kuroiwa K, Tatsugami K, Uchiumi T, Oda Y, Naito S. Antioxidant therapy alleviates oxidative stress by androgen deprivation and prevents conversion from androgen dependent to castration resistant prostate cancer. The Journal of urology. 2012 Feb 1;187(2):707-14.29. Patel SD, Waltham M, Wadoodi A, Burnand KG, Smith A. The role of endothelial cells and their progenitors in intimal hyperplasia. Therapeutic advances in cardiovascular disease. 2010 Apr;4(2):129-41.30. Sadasivam K, Nagarajan P, Durai I, Sundari M, Ayyavoo S. Carotid artery intima-media thickness in young adults with family history of coronary artery disease. Journal of Clinical and Diagnostic Research. 2015 9(9):01-04.31. Ellul J, Talelli P, Terzis G, Chrysanthopoulou A, Gioldasis G, Papapetropoulos T. Is the common carotid artery intima–media thickness associated with functional outcome after acute ischaemic stroke?. Journal of Neurology, Neurosurgery & Psychiatry. 2004 Aug 1;75(8):1197-9.32. Yeap BB, Hyde Z, Almeida OP, Norman PE, Chubb SP, Jamrozik K, Flicker L, Hankey GJ. Lower testosterone levels predict incident stroke and transient ischemic attack in older men. The Journal of Clinical Endocrinology & Metabolism. 2009 Jul 1;94(7):2353-9.33. Oskui PM, French WJ, Herring MJ, Mayeda GS, Burstein S, Kloner RA. Testosterone and the cardiovascular system: a comprehensive review of the clinical literature. Journal of the American Heart Association. 2013 Dec 19;2(6):e000272.34. Kalinchenko S, Zemlyanoy A, Gooren LJ. Improvement of the diabetic foot upon testosterone administration to hypogonadal men with peripheral arterial disease. Report of three cases. Cardiovascular diabetology. 2009 Dec;8(1):19.