27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen

Nature Medicine

Volumn 13, Issue 10, 2007, Pages 1185-1192

  Umetani, Michihisa ^a   Domoto, Hideharu ^a   Gormley, Andrew K ^b   Yuhanna, Ivan S ^b   Cummins, Carolyn L ^a   Javitt, Norman B ^c   Korach, Kenneth S ^d   Shaul, Philip W ^b   Mangelsdorf, David J ^a  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^c NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

26 HYDROXYCHOLESTEROL; CHOLESTEROL; CYP7B1; DRUG METABOLITE; ENZYME; ESTROGEN; ESTROGEN RECEPTOR; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; AORTA; ARTICLE; ATHEROSCLEROSIS; CARDIOVASCULAR EFFECT; CAROTID ARTERY; CELL TYPE; DIET; DRUG INHIBITION; DRUG MECHANISM; FEMALE; GENETIC MANIPULATION; HYPERCHOLESTEROLEMIA; KNOCKOUT GENE; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; VASCULAR DISEASE; VASCULARIZATION; VASODILATATION;

ANIMALS; AORTA, THORACIC; BINDING, COMPETITIVE; CARDIOTONIC AGENTS; CELL CULTURE TECHNIQUES; CELL LINE; CELLS, CULTURED; CHOLESTEROL, DIETARY; DNA, COMPLEMENTARY; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; ESTROGENS; FEMALE; GLUTATHIONE TRANSFERASE; HUMANS; HYDROXYCHOLESTEROLS; INHIBITORY CONCENTRATION 50; INJECTIONS, SUBCUTANEOUS; KIDNEY; KINETICS; MALE; MICE; MICE, KNOCKOUT; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE II; RECEPTORS, ESTROGEN; RECOMBINANT FUSION PROTEINS; RNA, MESSENGER; SELECTIVE ESTROGEN RECEPTOR MODULATORS; VASODILATION;

MUS; RATTUS;

EID: 34948820661     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm1641     Document Type: Article

References (49)

1. Deroo, B.J. & Korach, K.S. Estrogen receptors and human disease. J. Clin. Invest. 116, 561-570 (2006).
2. Mendelsohn, M.E. & Karas, R.H. The protective effects of estrogen on the cardiovascular system. N. Engl. J. Med. 340, 1801-1811 (1999).
3. Lindner, V. et al. Increased expression of estrogen receptor-beta mRNA in male blood vessels after vascular injury. Circ. Res. 83, 224-229 (1998).
4. Brouchet, L. et al. Estradiol accelerates reendothelialization in mouse carotid artery through estrogen receptor-alpha but not estrogen receptor-beta. Circulation 103, 423-428 (2001).
5. Pare, G. et al. Estrogen receptor-alpha mediates the protective effects of estrogen against vascular injury. Circ. Res. 90, 1087-1092 (2002).
6. Zhu, Y. et al. Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta. Science 295, 505-508 (2002).
7. Hodgin, J.B. & Maeda, N. Minireview: estrogen and mouse models of atherosclerosis. Endocrinology 143, 4495-4501 (2002).
8. Mendelsohn, M.E. & Karas, R.H. Molecular and cellular basis of cardiovascular gender differences. Science 308, 1583-1587 (2005).
9. Colditz, G.A. et al. Menopause and the risk of coronary heart disease in women. N. Engl. J. Med. 316, 1105-1110 (1987).
10. Turgeon, J.L., McDonnell, D.P., Martin, K.A. & Wise, P.M. Hormone therapy: physiological complexity belies therapeutic simplicity. Science 304, 1269-1273 (2004).
11. Karas, R.H. Current controversies regarding the cardiovascular effects of hormone therapy. Clin. Obstet. Gynecol. 47, 489-499 (2004).
12. Hulley, S. et al. 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. J. Am. Med. Assoc. 280, 605-613 (1998).
13. Rossouw, J.E. et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. J. Am. Med. Assoc. 288, 321-333 (2002).
14. Clark, J.H. A critique of Women's Health Initiative studies (2002-2006). Nucl. Recept. Signal. [online] 4, e023 (2006).
15. Brown, A.J. & Jessup, W. Oxysterols and atherosclerosis. Atherosclerosis 142, 1-28 (1999).
16. Schroepfer, G.J., Jr. Oxysterols: modulators of cholesterol metabolism and other processes. Physiol. Rev. 80, 361-554 (2000).
17. Russell, D.W. Oxysterol biosynthetic enzymes. Biochim. Biophys. Acta 1529, 126-135 (2000).
18. Janowski, B.A. et al. Structural requirements of ligands for the oxysterol liver X receptors LXRα and LXRβ. Proc. Natl. Acad. Sci. USA 96, 266-271 (1999).
19. Dzeletovic, S., Breuer, O., Lund, E. & Diczfalusy, U. Determination of cholesterol oxidation products in human plasma by isotope dilution-mass spectrometry. Anal. Biochem. 225, 73-80 (1995).
20. Garcia-Cruset, S., Carpenter, K.L., Guardiola, F., Stein, B.K. & Mitchinson, M.J. Oxysterol profiles of normal human arteries, fatty streaks and advanced lesions. Free Radic. Res. 35, 31-41 (2001).
21. Upston, J.M. et al. Disease stage-dependent accumulation of lipid and protein oxidation products in human atherosclerosis. Am. J. Pathol. 160, 701-710 (2002).
22. Crisby, M., Nilsson, J., Kostulas, V., Bjorkhem, I. & Diczfalusy, U. Localization of sterol 27-hydroxylase immuno-reactivity in human atherosclerotic plaques. Biochim. Biophys. Acta 1344, 278-285 (1997).
23. Li-Hawkins, J., Lund, E.G., Turley, S.D. & Russell, D.W. Disruption of the oxysterol 7alpha-hydroxylase gene in mice. J. Biol. Chem. 275, 16536-16542 (2000).
24. Christopherson, K.S. & Bredt, D.S. Nitric oxide in excitable tissues: physiological roles and disease. J. Clin. Invest. 100, 2424-2429 (1997).
25. Papapetropoulos, A., Rudic, R.D. & Sessa, W.C. Molecular control of nitric oxide synthases in the cardiovascular system. Cardiovasc. Res. 43, 509-520 (1999).
26. Li, H. & Forstermann, U. Nitric oxide in the pathogenesis of vascular disease. J. Pathol. 190, 244-254 (2000).
27. Chambliss, K.L. & Shaul, P.W. Estrogen modulation of endothelial nitric oxide synthase. Endocr. Rev. 23, 665-686 (2002).
28. Takahashi, K. et al. Both estrogen and raloxifene cause G1 arrest of vascular smooth muscle cells. J. Endocrinol. 178, 319-329 (2003).
29. Ravi, J., Mantzoros, C.S., Prabhu, A.S., Ram, J.L. & Sowers, J.R. In vitro relaxation of phenylephrine- and angiotensin II-contracted aortic rings by beta-estradiol. Am. J. Hypertens. 7, 1065-1069 (1994).
30. Parker, M.G., Arbuckle, N., Dauvois, S., Danielian, P. & White, R. Structure and function of the estrogen receptor. Ann. NY Acad. Sci. 684, 119-126 (1993).
31. Yu, L., Cao, G., Repa, J. & Stangl, H. Sterol regulation of scavenger receptor class B type I in macrophages. J. Lipid Res. 45, 889-899 (2004).
32. Yuhanna, I.S. et al. High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat. Med. 7, 853-857 (2001).
33. Iwakura, A. et al. Estrogen-mediated, endothelial nitric oxide synthase-dependent mobilization of bone marrow-derived endothelial progenitor cells contributes to reendothelialization after arterial injury. Circulation 108, 3115-3121 (2003).
34. Omoto, Y., Lathe, R., Warner, M. & Gustafsson, J.A. Early onset of puberty and early ovarian failure in CYP7B1 knockout mice. Proc. Natl. Acad. Sci. USA 102, 2814-2819 (2005).
35. Brzozowski, A.M. et al. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389, 753-758 (1997).
36. Shiau, A.K. et al. Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism. Nat. Struct. Biol. 9, 359-364 (2002).
37. Rubanyi, G.M. et al. Vascular estrogen receptors and endothelium-derived nitric oxide production in the mouse aorta. Gender difference and effect of estrogen receptor gene disruption. J. Clin. Invest. 99, 2429-2437 (1997).
38. Rosenfeld, M.E. et al. Estrogen inhibits the initiation of fatty streaks throughout the vasculature but does not inhibit intra-plaque hemorrhage and the progression of established lesions in apolipoprotein E deficient mice. Atherosclerosis 164, 251-259 (2002).
39. Hanke, H. et al. Effect of 17-beta estradiol on pre-existing atherosclerotic lesions: role of the endothelium. Atherosclerosis 147, 123-132 (1999).
40. Clarkson, T.B. & Appt, S.E. Controversies about HRT-lessons from monkey models. Maturitas 51, 64-74 (2005).
41. Grodstein, F., Clarkson, T.B. & Manson, J.E. Understanding the divergent data on postmenopausal hormone therapy. N. Engl. J. Med. 348, 645-650 (2003).
42. Herrington, D.M. et al. Statin therapy, cardiovascular events, and total mortality in the Heart and Estrogen/Progestin Replacement Study (HERS). Circulation 105, 2962-2967 (2002).
43. Makishima, M. et al. Vitamin D receptor as an intestinal bile acid sensor. Science 296, 1313-1316 (2002).
44. Klinge, C.M. Estrogen receptor interaction with estrogen response elements. Nucleic Acids Res. 29, 2905-2919 (2001).
45. Seetharam, D. et al. High-density lipoprotein promotes endothelial cell migration and reendothelialization via scavenger receptor-B type I. Circ. Res. 98, 63-72 (2006).
46. Couse, J.F., Yates, M.M., Walker, V.R. & Korach, K.S. Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) Null mice reveals hypergonadism and endocrine sex reversal in females lacking ERα but not ERβ. Mol. Endocrinol. 17, 1039-1053 (2003).
47. Repa, J.J. et al. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 289, 1524-1529 (2000).
48. Lund, E.G. & Diczfalusy, U. Quantitation of receptor ligands by mass spectrometry. Methods Enzymol. 364, 24-37 (2003).
49. Bookout, A.L. & Mangelsdorf, D.J. Quantitative real-time PCR protocol for analysis of nuclear receptor signaling pathways. Nucl. Recept. Signal. [online] 1, e012 (2003).