Hormonal effects on blood vessels

Hypertension Research

Volumn 35, Issue 4, 2012, Pages 363-369

  Akishita, Masahiro ^a   Yu, Jing ^a  

^a UNIVERSITY OF TOKYO   (Japan)

Author keywords

cardiovascular disease; endothelium; estrogen; testosterone; vascular smooth muscle

Indexed keywords

ANDROGEN RECEPTOR; ANDROSTANOLONE; BARIUM CHLORIDE; CONJUGATED ESTROGEN; CONJUGATED ESTROGEN PLUS MEDROXYPROGESTERONE ACETATE; ESTRADIOL; ESTROGEN; ESTROGEN RECEPTOR; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; G PROTEIN COUPLED RECEPTOR 30; NITRIC OXIDE; PLACEBO; SEX HORMONE; TESTOSTERONE; TESTOSTERONE UNDECANOATE;

ACUTE HEART INFARCTION; ANDROGEN THERAPY; ANTIOXIDANT ACTIVITY; ARTERIAL WALL THICKNESS; ATHEROSCLEROSIS; BLOOD SAMPLING; BLOOD VESSEL; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CARDIOVASCULAR SYSTEM; CLINICAL TRIAL (TOPIC); CORONARY ARTERY DISEASE; DISEASE MARKER; DRUG EFFICACY; DRUG MECHANISM; ECG ABNORMALITY; ENDOTHELIUM CELL; HORMONAL THERAPY; HORMONE ACTION; HUMAN; HYPOGONADISM; IN VITRO STUDY; IN VIVO STUDY; ISCHEMIC HEART DISEASE; LIPID METABOLISM; LIPID PEROXIDATION; MENOPAUSAL SYNDROME; META ANALYSIS; METABOLIC SYNDROME X; MORTALITY; NONHUMAN; OBESITY; PATHOPHYSIOLOGY; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SMOOTH MUSCLE FIBER; TESTOSTERONE BLOOD LEVEL; VASCULAR ENDOTHELIUM; VASCULAR SMOOTH MUSCLE; VASCULAR SMOOTH MUSCLE CELL; VASODILATATION;

BLOOD VESSELS; CARDIOVASCULAR DISEASES; ENDOTHELIUM, VASCULAR; ESTROGENS; FEMALE; HUMANS; MALE; MUSCLE, SMOOTH, VASCULAR; TESTOSTERONE;

EID: 84859595185     PISSN: 09169636     EISSN: 13484214     Source Type: Journal    
DOI: 10.1038/hr.2012.4     Document Type: Review

References (125)

1. Sitigler LH, Tulgan J. Treatment of angina pectoris by testosterone propionate. NY State J Med 1943; 43: 1424-1428.
2. Lesser MA. Testosterone propionate therapy in one hundred cases of angina pectoris. J Clin Endocrinol Metab 1946; 6: 549-557.
3. Barrett-Connor E. Sex differences in coronary heart disease. Why are women so superior? The 1995 Ancel Keys Lecture. Circulation 1997; 95: 252-264.
4. Reckelhoff JF. Gender differences in the regulation of blood pressure. Hypertension 2001; 37: 1199-1208. (Pubitemid 34163570)
5. Mendelsohn ME, Karas RH. Molecular and cellular basis of cardiovascular gender differences. Science 2005; 308: 1583-1587. (Pubitemid 40807497)
6. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998; 280: 605-613.
7. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288: 321-333. (Pubitemid 34761611)
8. Phillips GB, Pinkerbell BH, Jing TY. The association of hypotestosteronemia with coronary artery disease in men. Arterioscler Thromb 1994; 14: 701-706.
9. English KM, Mandour O, Steeds RP, Diver MJ, Jones TH, Channer KS. Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J 2000; 2: 890-894. (Pubitemid 30307417)
10. Rosano GM, Sheiban I, Massaro R, Pagnotta P, Marazzi G, Vitale C, Mercuro G, Volterrani M, Aversa A, Fini M. Low testosterone levels are associated with coronary artery disease in male patients with angina. Int J Impot Res 2007; 19: 176-182. (Pubitemid 46340835)
11. Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med 1999; 340: 1801-1811. (Pubitemid 29266405)
12. Klouche M. Estrogens in human vascular diseases. Ann NY Acad Sci 2006; 1089: 431-443. (Pubitemid 47092087)
13. Yang XP, Reckelhoff JF. Estrogen, hormonal replacement therapy and cardiovascular disease. Curr Opin Nephrol Hypertens 2011; 20: 133-138.
14. Mendelsohn ME, Karas RH. Rapid progress for non-nuclear estrogen receptor signaling. J Clin Invest 2010; 120: 2277-2279.
15. Yamakawa-Kobayashi K, Somekawa Y, Fujimura M, Tomura S, Arinami T, Hamaguchi H. Relation of the -514C/T polymorphism in the hepatic lipase gene to serum HDL and LDL cholesterol levels in postmenopausal women under hormone replacement therapy. Atherosclerosis 2002; 162: 17-21. (Pubitemid 34327337)
16. Kuohung W, Shwaery GT, Keaney Jr JF. Tamoxifen, esterified estradiol, and physiologic concentrations of estradiol inhibit oxidation of low-density lipoprotein by endothelial cells. Am J Obstet Gynecol 2001; 184: 1060-1063. (Pubitemid 32434242)
17. Santanam N, Shern-Brewer R, McClatchey R, Castellano PZ, Murphy AA, Voelkel S, Parthasarathy S. Estradiol as an antioxidant: incompatible with its physiological concentrations and function. J Lipid Res 1998; 39: 2111-2118. (Pubitemid 28523116)
18. Liang YQ, Akishita M, Kim S, Ako J, Hashimoto M, Iijima K, Ohike Y, Watanabe T, Sudoh N, Toba K, Yoshizumi M, Ouchi Y. Estrogen receptor beta is involved in the anorectic action of estrogen. Int J Obes Relat Metab Disord 2002; 26: 1103-1109.
19. Lijnen HR. Murine models of obesity and hormonal therapy. Thromb Res 2011; 127 (Suppl 3): S17-S20.
20. Kauser K, Rubanyi GM. Potential cellular signaling mechanisms mediating upregulation of endothelial nitric oxide production by estrogen. J Vasc Res 1997; 34: 229-236. (Pubitemid 27281698)
21. Hashimoto M, Akishita M, Eto M, Ishikawa M, Kozaki K, Toba K, Sagara Y, Taketani Y, Orimo H, Ouchi Y. Modulation of endothelium-dependent flow-mediated dilatation of the brachial artery by sex and menstrual cycle. Circulation 1995; 92: 3431-3435.
22. Geary GG, Krause DN, Duckles SP. Estrogen reduces mouse cerebral artery tone through endothelial NOS- and cyclooxygenase-dependent mechanisms. Am J Physiol Heart Circ Physiol 2000; 279: H511-H519.
23. Liu MY, Hattori Y, Fukao M, Sato A, Sakuma I, Kanno M. Alterations in EDHF-mediated hyperpolarization and relaxation in mesenteric arteries of female rats in long-term deficiency of oestrogen and during oestrus cycle. Br J Pharmacol 2001; 132: 1035-1046. (Pubitemid 32238909)
24. Jun SS, Chen Z, Pace MC, Shaul PW. Estrogen upregulates cyclooxygenase-1 gene expression in ovine fetal pulmonary artery endothelium. J Clin Invest 1998; 102: 176-183. (Pubitemid 28323844)
25. Sherman TS, Chambliss KL, Gibson LL, Pace MC, Mendelsohn ME, Pfister SL, Shaul PW. Estrogen acutely activates prostacyclin synthesis in ovine fetal pulmonary artery endothelium. Am J Respir Cell Mol Biol 2002; 26: 610-616. (Pubitemid 34315870)
26. Akishita M, Kozaki K, Eto M, Yoshizumi M, Ishikawa M, Toba K, Orimo H, Ouchi Y. Estrogen attenuates endothelin-1 production by bovine endothelial cells via estrogen receptor. Biochem Biophys Res Commun 1998; 251: 17-21. (Pubitemid 28498056)
27. Han SZ, Karaki H, Ouchi Y, Akishita M, Orimo H. 17 Beta-estradiol inhibits Ca2+ influx and Ca2+ release induced by thromboxane A2 in porcine coronary artery. Circulation 1995; 91: 2619-2626.
28. Crews JK, Khalil RA. Antagonistic effects of 17 beta-estradiol, progesterone, and testosterone on Ca2+ entry mechanisms of coronary vasoconstriction. Arterioscler Thromb Vasc Biol 1999; 19: 1034-1040. (Pubitemid 29177353)
29. Prakash YS, Togaibayeva AA, Kannan MS, Miller VM, Fitzpatrick LA, Sieck GC. Estrogen increases Ca2+ efflux from female porcine coronary arterial smooth muscle. Am J Physiol 1999; 276: H926-H934. (Pubitemid 29157465)
30. Chen SJ, Li H, Durand J, Oparil S, Chen YF. Estrogen reduces myointimal proliferation after balloon injury of rat carotid artery. Circulation 1996; 93: 577-584. (Pubitemid 26043619)
31. Krom YD, Pires NM, Jukema JW, de Vries MR, Frants RR, Havekes LM, van Dijk KW, Quax PH. Inhibition of neointima formation by local delivery of estrogen receptor alpha and beta specific agonists. Cardiovasc Res 2007; 73: 217-226. (Pubitemid 44937195)
32. Akishita M, Ouchi Y, Miyoshi H, Kozaki K, Inoue S, Ishikawa M, Eto M, Toba K, Orimo H. Estrogen inhibits cuff-induced intimal thickening of rat femoral artery: effects on migration and proliferation of vascular smooth muscle cells. Atherosclerosis 1997; 130: 1-10. (Pubitemid 27158023)
33. Krasinski K, Spyridopoulos I, Asahara T, van der Zee R, Isner JM, Losordo DW. Estradiol accelerates functional endothelial recovery after arterial injury. Circulation 1997; 95: 1768-1772. (Pubitemid 27164391)
34. Sudoh N, Toba K, Akishita M, Ako J, Hashimoto M, Iijima K, Kim S, Liang YQ, Ohike Y, Watanabe T, Yamazaki I, Yoshizumi M, Eto M, Ouchi Y. Estrogen prevents oxidative stress-induced endothelial cell apoptosis in rats. Circulation 2001; 103: 724-729. (Pubitemid 32144202)
35. Simoncini T, Hafezi-Moghadam A, Brazil DP, Ley K, Chin WW, Liao JK. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 2000; 407: 538-541.
36. Haas E, Meyer MR, Schurr U, Bhattacharya I, Minotti R, Nguyen HH, Heigl A, Lachat M, Genoni M, Barton M. Differential effects of 17beta-estradiol on function and expression of estrogen receptor alpha, estrogen receptor beta, and GPR30 in arteries and veins of patients with atherosclerosis. Hypertension 2007; 49: 1358-1363. (Pubitemid 46809380)
37. Haas E, Bhattacharya I, Brailoiu E, Damjanović M, Brailoiu GC, Gao X, Mueller-Guerre L, Marjon NA, Gut A, Minotti R, Meyer MR, Amann K, Ammann E, Perez-Dominguez A, Genoni M, Clegg DJ, Dun NJ, Resta TC, Prossnitz ER, Barton M. Regulatory role of G protein-coupled estrogen receptor for vascular function and obesity. Circ Res 2009; 104: 288-291.
38. Meyer MR, Prossnitz ER, Barton M. The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function. Vascul Pharmacol 2011; 55: 17-25.
39. Broughton BR, Miller AA, Sobey CG. Endothelium-dependent relaxation by G protein-coupled receptor 30 agonists in rat carotid arteries. Am J Physiol Heart Circ Physiol 2010; 298: H1055-H1061.
40. Lindsey SH, Carver KA, Prossnitz ER, Chappell MC. Vasodilation in response to the GPR30 agonist G-1 is not different from estradiol in the mRen2. Lewis female rat. J Cardiovasc Pharmacol 2011; 57: 598-603.
41. Meyer MR, Baretella O, Prossnitz ER, Barton M. Dilation of epicardial coronary arteries by the G protein-coupled estrogen receptor agonists G-1 and ICI 182,780. Pharmacology 2010; 86: 58-64.
42. Takahashi K, Ohmichi M, Yoshida M, Hisamoto K, Mabuchi S, Arimoto-Ishida E, Mori A, Tsutsumi S, Tasaka K, Murata Y, Kurachi H. Both estrogen and raloxifene cause G1 arrest of vascular smooth muscle cells. J Endocrinol 2003; 178: 319-329. (Pubitemid 37063073)
43. Rowlands DJ, Chapple S, Siow RC, Mann GE. Equol-stimulated mitochondrial reactive oxygen species activate endothelial nitric oxide synthase and redox signaling in endothelial cells: roles for F-actin and GPR30. Hypertension 2011; 57: 833-840.
44. Deschamps AM, Murphy E, Sun J. Estrogen receptor activation and cardioprotection in ischemia reperfusion injury. Trends Cardiovasc Med 2010; 20: 73-78.
45. Filice E, Recchia AG, Pellegrino D, Angelone T, Maggiolini M, Cerra MC. A new membrane G protein-coupled receptor (GPR30) is involved in the cardiac effects of 17beta-estradiol in the male rat. J Physiol Pharmacol 2009; 60: 3-10.
46. Prossnitz ER, Maggiolini M. Mechanisms of estrogen signaling and gene expression via GPR30. Mol Cell Endocrinol 2009; 308: 32-38.
47. Prossnitz ER, Barton M. The G-protein-coupled estrogen receptor GPER in health and disease. Nat Rev Endocrinol 2011; 7: 715-726.
48. Grodstein F, Stampfer MJ, Colditz GA, Willett WC, Manson JE, Joffe M, Rosner B, Fuchs C, Hankinson SE, Hunter DJ, Hennekens CH, Speizer FE. Postmenopausal hormone therapy and mortality. N Engl J Med 1997; 336: 1769-1775.
49. Grodstein F, Manson JE, Colditz GA, Willett WC, Speizer FE, Stampfer MJ. A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann Intern Med 2000; 133: 933-941. (Pubitemid 32003509)
50. Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, Ko M, LaCroix AZ, Margolis KL, Stefanick ML. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007; 297: 1465-1477. (Pubitemid 46556472)
51. Salpeter SR, Cheng J, Thabane L, Buckley NS, Salpeter EE. Bayesian meta-analysis of hormone therapy and mortality in younger postmenopausal women. Am J Med 2009; 122: 1016-1022.
52. Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD, Hsia J, Kuller LH, Cochrane BB, Hunt JR, Ludlam SE, Pettinger MB, Gass M, Margolis KL, Nathan L, Ockene JK, Prentice RL, Robbins J, Stefanick ML. Estrogen therapy and coronary-artery calcification. N Engl J Med 2007; 356: 2591-2602. (Pubitemid 46961004)
53. Miller VM, Black DM, Brinton EA, Budoff MJ, Cedars MI, Hodis HN, Lobo RA, Manson JE, Merriam GR, Naftolin F, Santoro N, Taylor HS, Harman SM. Using basic science to design a clinical trial: baseline characteristics of women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). J Cardiovasc Transl Res 2009; 2: 228-239.
54. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men: Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001; 86: 724-731. (Pubitemid 32207487)
55. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ, McKinlay JB. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2002; 87: 589-598. (Pubitemid 34158223)
56. Lamberts SW, van den Beld AW, van der Lely AJ. The endocrinology of aging. Science 1997; 278: 419-424. (Pubitemid 27454418)
57. Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005; 26: 833-876. (Pubitemid 41428540)
58. Sewdarsen M, Vythilingum S, Jialal I, Desai RK, Becker P. Abnormalities in sex hormones are a risk factor for premature manifestation of coronary artery disease in South African Indian men. Atherosclerosis 1990; 83: 111-117. (Pubitemid 20237869)
59. Mohamad MJ, Mohammad MA, Karayyem M, Hairi A, Hader AA. Serum levels of sex hormones in men with acute myocardial infarction. Neuro Endocrinol Lett 2007; 28: 182-186. (Pubitemid 46739070)
60. Feldman HA, Johannes CB, McKinlay JB, Longcope C. Low dehydroepiandrosterone sulfate and heart disease in middle-aged men: cross-sectional results from the Massachusetts Male Aging Study. Ann Epidemiol 1998; 8: 217-228. (Pubitemid 28208939)
61. 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: 2694-2701. (Pubitemid 350291241)
62. Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab 2008; 93: 68-75.
63. Vikan T, Schirmer H, Njølstad I, Svartberg J. Endogenous sex hormones and the prospective association with cardiovascular disease and mortality in men: the Tromsø Study. Eur J Endocrinol 2009; 161: 435-442.
64. Akishita M, Hashimoto M, Ohike Y, Ogawa S, Iijima K, Eto M, Ouchi Y. Low testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors. Atherosclerosis 2010; 210: 232-236.
65. Muller M, van de Beld AW, Bots ML, Grobbee DE, Lamberts SWJ, van der Schouw YT. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation 2004; 109: 2074-2079. (Pubitemid 38620214)
66. Van de Beld AW, Bots ML, Janssen JAMLL, Pols HAP, Lamberts SWJ, Grobbee DE. Endogenous hormones and carotid atherosclerosis in elderly men. Am J Epidemiol 2003; 157: 25-31. (Pubitemid 36043733)
67. Makinen J, Jarvisalo MJ, Pollanen P, Perheentupa A, Irjala K, Koskenvuo M, Makinen J, Huhtaniemi I, Raitakari OT. Increased carotid atherosclerosis in andropausal middle-aged men. J Am Coll Cardiol 2005; 45: 1603-1608. (Pubitemid 40704493)
68. Demirbag R, Yilmaz R, Ulucay A, Unlu D. The inverse relationship between thoracic aortic intima media thickness and testosterone level. Endocr Res 2005; 31: 335-344. (Pubitemid 43207228)
69. Hak AE, Witteman JC, de Jong FH, Geerlings MI, Hofman A, Pols HA. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. J Clin Endocrinol Metab 2002; 87: 3632-3639. (Pubitemid 34879505)
70. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 2010; 55: 1318-1327.
71. Yaron M, Greenman Y, Rosenfeld JB, Izkhakov E, Limor R, Osher E, Shenkerman G, Tordjman K, Stern N. Effect of testosterone replacement therapy on arterial stiffness in older hypogonadal men. Eur J Endocrinol 2009; 160: 839-846.
72. Kyriazis J, Tzanakis I, Stylianou K, Katsipi I, Moisiadis D, Papadaki A, Mavroeidi V, Kagia S, Karkavitsas N, Daphnis E. Low serum testosterone, arterial stiffness and mortality in male haemodialysis patients. Nephrol Dial Transplant 2011; 26: 2971-2977.
73. Akishita M, Hashimoto M, Ohike Y, Ogawa S, Iijima K, Eto M, Ouchi Y. Low testosterone level is an independent determinant of endothelial dysfunction in men. Hypertens Res 2007; 30: 1029-1034.
74. Mäkinen JI, Perheentupa A, Irjala K, Pöllänen P, Mäkinen J, Huhtaniemi I, Raitakari OT. Endogenous testosterone and brachial artery endothelial function in middle-aged men with symptoms of late-onset hypogonadism. Aging Male 2011; 14: 237-242.
75. Yilmaz MI, Sonmez A, Qureshi AR, Saglam M, Stenvinkel P, Yaman H, Eyileten T, Caglar K, Oguz Y, Taslipinar A, Vural A, Gok M, Unal HU, Yenicesu M, Carrero JJ. Endogenous testosterone, endothelial dysfunction, and cardiovascular events in men with nondialysis chronic kidney disease. Clin J Am Soc Nephrol 2011; 6: 1617-1625.
76. Webb CM, McNeill JG, Hayward CS, de Zeigler D, Collins P. Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation 1999; 100: 1690-1696. (Pubitemid 29485250)
77. Rosano GM, Leonardo F, Pagnotta P, Pelliccia F, Panina G, Cerquetani E, della Monica PL, Bonfigli B, Volpe M, Chierchia SL. Acute anti-ischemic effect of testosterone in men with coronary artery disease. Circulation 1999; 99: 1666-1670. (Pubitemid 29162477)
78. Webb CM, Adamson DL, de Zeigler D, Collins P. Effect of acute testosterone on myocardial ischemia in men with coronary artery disease. Am J Cardiol 1999; 83: 437-439. (Pubitemid 29066505)
79. Pugh PJ, Jones TH, Channer KS. Acute haemodynamic effects of testosterone in men with chronic heart failure. Eur Heart J 2003; 24: 909-915. (Pubitemid 36559984)
80. Malkin CJ, Pugh PJ, West JN, van Beek EJ, Jones TH, Channer KS. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Eur Heart J 2006; 27: 57-64. (Pubitemid 41785933)
81. Webb CM, Elkington AG, Kraidly MM, Keenan N, Pennell DJ, Collins P. Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease. Am J Cardiol 2008; 101: 618-624. (Pubitemid 351625084)
82. Ong PJ, Patrizi G, Chong WC, Webb CM, Hayward CS, Collins P. Testosterone enhances flow-mediated brachial artery reactivity in men with coronary artery disease. Am J Cardiol 2000; 85: 269-272. (Pubitemid 30026117)
83. Kang SM, Jang Y, Kim JY, Chung N, Cho SY, Chae JS, Lee JH. Effect of oral administration of testosterone on brachial arterial vasoreactivity in men with coronary artery disease. Am J Cardiol 2002; 89: 862-864. (Pubitemid 34241469)
84. Corrales JJ, Almeida M, Burgo R, Mories MT, Miralles JM, Orfao A. Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency. J Endocrinol 2006; 189: 595-604. (Pubitemid 43922123)
85. Kalinchenko SY, Tishova YA, Mskhalaya GJ, Gooren LJ, Giltay EJ, Saad F. Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebocontrolled Moscow study. Clin Endocrinol (Oxf) 2010; 73: 602-612.
86. Haddad RM, Kennedy CC, Caples SM, Tracz MJ, Boloña ER, Sideras K, Uraga MV, Erwin PJ, Montori VM. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc 2007; 82: 29-39. (Pubitemid 46036319)
87. Traish AM, Miner MM, Morgentaler A, Zitzmann M. Testosterone deficiency. Am J Med 2011; 124: 578-587.
88. Corona G, Rastrelli G, Vignozzi L, Mannucci E, Maggi M. Testosterone, cardiovascular disease and the metabolic syndrome. Best Pract Res Clin Endocrinol Metab 2011; 25: 337-353.
89. Yu J, Akishita M, Eto M, Ogawa S, Son BK, Kato S, Ouchi Y, Okabe T. Androgen receptor-dependent activation of endothelial nitric oxide synthase in vascular endothelial cells: role of phosphatidylinositol 3-kinase/AKT pathway. Endocrinology 2010; 151: 1822-1828.
90. Son BK, Akishita M, Iijima K, Ogawa S, Maemura K, Yu J, Takeyama K, Kato S, Eto M, Ouchi Y. Androgen receptor-dependent transactivation of growth arrest-specific gene 6 mediates inhibitory effects of testosterone on vascular calcification. J Biol Chem 2010; 285: 7537-7544.
91. Qiu Y, Yanase T, Hu H, Tanaka T, Nishi Y, Liu M, Sueishi K, Sawamura T, Nawata H. Dihydrotestosterone suppresses foam cell formation and attenuates atherosclerosis development. Endocrinology 2010; 151: 3307-3316.
92. Bruck B, Brehme U, Gugel N, Hanke S, Finking G, Lutz C, Benda N, Schmahl FW, Haasis R, Hanke H. Gender-specific differences in the effects of testosterone and estrogen on the development of atherosclerosis in rabbits. Arterioscler Thromb Vasc Biol 1997; 17: 2192-2199. (Pubitemid 28057121)
93. 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: 813-819. (Pubitemid 29181488)
94. Tharp DL, Masseau I, Ivey J, Ganjam VK, Bowles DK. Endogenous testosterone attenuates neointima formation after moderate coronary balloon injury in male swine. Cardiovasc Res 2009; 82: 152-160.
95. Nathan L, Shi W, Dinh H, Mukherjee TK, Wang X, Lusis AJ, Chaudhuri G. Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase. Proc Natl Acad Sci 2001; 98: 3589-3593. (Pubitemid 32220889)
96. 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: 2857-2864.
97. Bourghardt J, Wilhelmson AS, Alexanderson C, De Gendt K, Verhoeven G, Krettek A, Ohlsson C, Tivesten A. Androgen receptor-dependent and independent atheroprotection by testosterone in male mice. Endocrinology 2010; 151: 5428-5437.
98. Cai J, Hong Y, Weng C, Tan C, Imperato-McGinley J, Zhu YS. Androgen stimulates endothelial cell proliferation via an androgen receptor/VEGF/cyclin A-mediated mechanism. Am J Physiol Heart Circ Physiol 2011; 300: H1210-H1221.
99. Foresta C, Caretta N, Lana A, De Toni L, Biagioli A, Ferlin A, Garolla A. Reduced number of circulating endothelial progenitor cells in hypogonadal men. J Clin Endocrinol Metab 2006; 91: 4599-4602. (Pubitemid 44833444)
100. Foresta C, Zuccarello D, De Toni L, Garolla A, Caretta N, Ferlin A. Androgens stimulate endothelial progenitor cells through an androgen-mediated pathway. Clin Endo 2008; 68: 284-289.
101. Costarella CE, Stallone JN, Rutecki GW, Whittier FC. Testosterone causes direct relaxation of rat thoracic aorta. J Pharmacol Exp Ther 1996; 277: 34-39. (Pubitemid 27169040)
102. Pearson LJ, Yandle TG, Nicholls MG, Evans JJ. Regulation of endothelin-1 release from human endothelial cells by sex steroids and angiotensin-II. Peptides 2008; 9: 1057-1061.
103. Jin H, Lin J, Fu L, Mei YF, Peng G, Tan X, Wang DM, Wang W, Li YG. Physiological testosterone stimulates tissue plasminogen activator and tissue factor pathway inhibitor and inhibits plasminogen activator inhibitor type 1 release in endothelial cells. Biochem Cell Biol 2007; 85: 246-251. (Pubitemid 46841694)
104. Yue P, Chatterjee K, Beale C, Poole-Wilson PA, Collins P. Testosterone relaxes rabbit coronary arteries and aorta. Circulation 1995; 91: 1154-1160.
105. Hall J, Jones RD, Jones TH, Channer KS, Peers C. Selective inhibition of L-type Ca2+ channels in A7r5 cells by physiological levels of testosterone. Endocrinology 2006; 147: 2675-2680. (Pubitemid 43764603)
106. Jones RD, English KM, Jones TH, Channer KS. Testosterone-induced coronary vasodilatation occurs via a non-genomic mechanism: evidence of a direct calcium antagonism action. Clin Sci (Lond) 2004; 107: 149-158. (Pubitemid 39070931)
107. Alvarez E, Cairrão E, Morgado M, Morais C, Verde I. Testosterone and cholesterol vasodilation of rat aorta involves L-type calcium channel inhibition. Adv Pharmacol Sci 2010; 2010: 534184.
108. Scragg JL, Jones RD, Channer KS, Jones TH, Peers C. Testosterone is a potent inhibitor of L-type Ca(2+) channels. Biochem Biophys Res Commun 2004; 318: 503-506. (Pubitemid 38553808)
109. Honda H, Unemoto T, Kogo H. Different mechanisms for testosterone-induced relaxation of aorta between normotensive and spontaneously hypertensive rats. Hypertension 1999; 34: 1232-1236. (Pubitemid 30002387)
110. Tep-areenan P, Kendall DA, Randall MD. Testosterone-induced vasorelaxation in the rat mesenteric arterial bed is mediated predominantly via potassium channels. Br J Pharmacol 2002; 135: 735-740. (Pubitemid 34177651)
111. Yildiz O, Seyrek M, Gul H, Un I, Yildirim V, Ozal E, Uzun M, Bolu E. Testosterone relaxes human internal mammary artery in vitro. J Cardiovasc Pharmacol 2005; 45: 580-585. (Pubitemid 40734580)
112. Cairrão E, Alvarez E, Santos-Silva AJ, Verde I. Potassium channels are involved in testosterone-induced vasorelaxation of human umbilical artery. Naunyn Schmiedebergs Arch Pharmacol 2008; 376: 375-383.
113. 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: 1382-1385. (Pubitemid 32220628)
114. Somjen D, Kohen F, Gayer B, Kulik T, Knoll E, Stern N. Role of putative membrane receptors in the effect of androgens on human vascular cell growth. J Endocrinol 2004; 180: 97-106. (Pubitemid 38180761)
115. Natoli AK, Medley TL, Ahimastos AA, Drew BG, Thearle DJ, Dilley RJ, Kingwell BA. Sex steroids modulate human aortic smooth muscle cell matrix protein deposition and matrix metalloproteinase expression. Hypertension 2005; 46: 1129-1134. (Pubitemid 41533015)
116. Masuda A, Mathur R, Halushka PV. Testosterone increases thromboxane A2 receptors in cultured rat aortic smooth muscle cells. Circ Res 1991; 69: 638-643.
117. Kumai T, Tanaka M, Watanabe M, Nakura H, Kobayashi S. Influence of androgen on tyrosine hydroxylase mRNA in adrenal medulla of spontaneously hypertensive rats. Hypertension 1995; 26: 208-212.
118. Reckelhoff JF, Zhang H, Granger JP. Testosterone exacerbates hypertension and reduces pressure-natriuresis in male spontaneously hypertensive rats. Hypertension 1998; 31: 435-439.
119. Kienitz T, Quinkler M. Testosterone and blood pressure regulation. Kidney Blood Press Res 2008; 31: 71-79. (Pubitemid 351630063)
120. Yanes LL, Sartori-Valinotti JC, Iliescu R, Romero DG, Racusen LC, Zhang H, Reckelhoff JF. Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats. Am J Physiol Renal Physiol 2009; 296: F771-F779.
121. Fernández-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, Agrwal N, Elamin MB, Gallegos-Orozco JF, Wang AT, Erwin PJ, Bhasin S, Montori VM. Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab 2010; 95: 2560-2575.
122. Longcope C, Franz C, Morello C, Baker R, Johnston Jr CC. Steroid and gonadotropin levels in women during the peri-menopausal years. Maturitas 1986; 8: 189-196. (Pubitemid 17170484)
123. Bernini GP, Sgró M, Moretti A, Argenio GF, Barlascini CO, Cristofani R, Salvetti A. Endogenous androgens and carotid intimal-medial thickness in women. J Clin Endocrinol Metab 1999; 84: 2008-2012. (Pubitemid 30647026)
124. Brand JS, van der Schouw YT. Testosterone, SHBG and cardiovascular health in postmenopausal women. Int J Impot Res 2010; 22: 91-104.
125. Saltiki K, Cimponeriu A, Garofalaki M, Sarika L, Papathoma A, Stamatelopoulos K, Alevizaki M. Severity of coronary artery disease in postmenopausal women: association with the androgen receptor gene (CAG)n repeat polymorphism. Menopause 2011; 18: 1225-1231.