Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation Research
Search: search_blue_button Advanced Search
Circulation Research. 1999;84:1285-1291

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Harada, N.
Right arrow Articles by Takagi, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Harada, N.
Right arrow Articles by Takagi, Y.
Related Collections
Right arrow Cell signalling/signal transduction
Right arrow Gene expression
Right arrow Smooth muscle proliferation and differentiation
(Circulation Research. 1999;84:1285-1291.)
© 1999 American Heart Association, Inc.


Original Contributions

Localized Expression of Aromatase in Human Vascular Tissues

Nobuhiro Harada, Hironobu Sasano, Hiroshi Murakami, Tsuneo Ohkuma, Hiroshi Nagura, Yasuyuki Takagi

From the Department of Biochemistry, Fujita Health University School of Medicine (N.H., Y.T.), Toyoake, and the Departments of Pathology (H.S., H.N.) and Surgery (H.M., T.O), Tohoku University School of Medicine, Sendai, Japan.

Correspondence to Nobuhiro Harada, PhD, Department of Biochemistry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. E-mail nharada{at}fujita-hu.ac.jp

Abstract—The atheroprotective effects of estrogen are well established and the presence of an estrogen receptor in vascular tissues has recently been reported. Therefore, we investigated the localization of the estrogen-producing enzyme aromatase in vascular tissues to assess the possible contribution of endocrine, paracrine, and autocrine modes of action. Aromatase was found in human vascular smooth muscle cells (SMCs) but not in endothelial cells on in situ hybridization. These observations were further supported by quantitative analysis of aromatase mRNA and the activity in 15 human vascular specimens. Only trace levels of expression were detected in the 3 infants examined, whereas 0.0088 to 0.0806 amol/µg RNA of aromatase mRNA and 12.9 to 122.3 fmol · h-1 · mg-1 protein of the activity were detected in 12 of the adult individuals. The switching of tissue-specific exon 1 of the human aromatase gene was also observed in some cases. Aromatase was found to be expressed only in cultured SMCs and not in cultured endothelial cells of human aorta and pulmonary artery and to be regulated through dexamethasone and the signaling pathways of protein kinase A and C. Study results revealed the localized expression of aromatase in vascular SMCs, which indicated a possible direct action of locally produced estrogen in an autocrine or paracrine manner, with possible cross talk between smooth muscle and endothelial cells.


Key Words: estrogen • aromatase • in situ hybridization • smooth muscle cell




This article has been cited by other articles:


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
T. Henriques, X. Zhang, F. B. Yiannikouris, A. Daugherty, and L. A. Cassis
Androgen Increases AT1a Receptor Expression in Abdominal Aortas to Promote Angiotensin II-Induced AAAs in Apolipoprotein E-Deficient Mice
Arterioscler Thromb Vasc Biol, July 1, 2008; 28(7): 1251 - 1256.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
D. Sun, C. Yan, A. Jacobson, H. Jiang, M. A. Carroll, and A. Huang
Contribution of epoxyeicosatrienoic acids to flow-induced dilation in arteries of male ER{alpha} knockout mice: role of aromatase
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1239 - R1246.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
G. Han, H. Ma, R. Chintala, K. Miyake, D. J. R. Fulton, S. A. Barman, and R. E. White
Nongenomic, endothelium-independent effects of estrogen on human coronary smooth muscle are mediated by type I (neuronal) NOS and PI3-kinase-Akt signaling
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H314 - H321.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
E. Haas, M. R. Meyer, U. Schurr, I. Bhattacharya, R. Minotti, H. H. Nguyen, A. Heigl, M. Lachat, M. Genoni, and M. Barton
Differential Effects of 17{beta}-Estradiol on Function and Expression of Estrogen Receptor {alpha}, Estrogen Receptor {beta}, and GPR30 in Arteries and Veins of Patients With Atherosclerosis
Hypertension, June 1, 2007; 49(6): 1358 - 1363.
[Abstract] [Full Text] [PDF]


Home page
Endocr. Rev.Home page
J. L. Turgeon, M. C. Carr, P. M. Maki, M. E. Mendelsohn, and P. M. Wise
Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies
Endocr. Rev., October 1, 2006; 27(6): 575 - 605.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
C. J. Pepine, W. W. Nichols, and D. F. Pauly
Estrogen and Different Aspects of Vascular Disease in Women and Men
Circ. Res., September 1, 2006; 99(5): 459 - 461.
[Full Text] [PDF]


Home page
HypertensionHome page
M. R. Meyer, E. Haas, and M. Barton
Gender Differences of Cardiovascular Disease: New Perspectives for Estrogen Receptor Signaling
Hypertension, June 1, 2006; 47(6): 1019 - 1026.
[Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
G. Han, X. Yu, L. Lu, S. Li, H. Ma, S. Zhu, X. Cui, and R. E. White
Estrogen Receptor {alpha} Mediates Acute Potassium Channel Stimulation in Human Coronary Artery Smooth Muscle Cells
J. Pharmacol. Exp. Ther., March 1, 2006; 316(3): 1025 - 1030.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
K. K. Maddali, D. H. Korzick, D. L. Tharp, and D. K. Bowles
PKC{delta} Mediates Testosterone-induced Increases in Coronary Smooth Muscle Cav1.2
J. Biol. Chem., December 30, 2005; 280(52): 43024 - 43029.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
R. E. White, G. Han, C. Dimitropoulou, S. Zhu, K. Miyake, D. Fulton, S. Dave, and S. A. Barman
Estrogen-induced contraction of coronary arteries is mediated by superoxide generated in vascular smooth muscle
Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1468 - H1475.
[Abstract] [Full Text] [PDF]


Home page
Hum Reprod UpdateHome page
L.M. Rivera-Woll, M. Papalia, S.R. Davis, and H.G. Burger
Androgen insufficiency in women: diagnostic and therapeutic implications
Hum. Reprod. Update, September 1, 2004; 10(5): 421 - 432.
[Abstract] [Full Text] [PDF]


Home page
Endocr. Rev.Home page
T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth
Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification
Endocr. Rev., August 1, 2004; 25(4): 629 - 672.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
A. Sierra-Ramirez, T. Morato, R. Campos, I. Rubio, C. Calzada, E. Mendez, and G. Ceballos
Acute effects of testosterone on intracellular Ca2+ kinetics in rat coronary endothelial cells are exerted via aromatization to estrogens
Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H63 - H71.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
A. Villablanca, D. Lubahn, L. Shelby, K. Lloyd, and S. Barthold
Susceptibility to Early Atherosclerosis in Male Mice Is Mediated by Estrogen Receptor {alpha}
Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 1055 - 1061.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
R. K. Dubey, S. P. Tofovic, and E. K. Jackson
Cardiovascular Pharmacology of Estradiol Metabolites
J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 403 - 409.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
M. E. Mendelsohn and G. M.C. Rosano
Hormonal Regulation of Normal Vascular Tone in Males
Circ. Res., December 12, 2003; 93(12): 1142 - 1145.
[Full Text] [PDF]


Home page
Am. J. Pathol.Home page
Y. Nakamura, Y. Miki, T. Suzuki, T. Nakata, A. D. Darnel, T. Moriya, C. Tazawa, H. Saito, T. Ishibashi, S. Takahashi, et al.
Steroid Sulfatase and Estrogen Sulfotransferase in the Atherosclerotic Human Aorta
Am. J. Pathol., October 1, 2003; 163(4): 1329 - 1339.
[Abstract] [Full Text] [PDF]


Home page
Endocr. Rev.Home page
P. Y. Liu, A. K. Death, and D. J. Handelsman
Androgens and Cardiovascular Disease
Endocr. Rev., June 1, 2003; 24(3): 313 - 340.
[Abstract] [Full Text] [PDF]


Home page
Endocr. Rev.Home page
F. C. W. Wu and A. von Eckardstein
Androgens and Coronary Artery Disease
Endocr. Rev., April 1, 2003; 24(2): 183 - 217.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
M. Zitzmann, M. Brune, and E. Nieschlag
Vascular Reactivity in Hypogonadal Men Is Reduced by Androgen Substitution
J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5030 - 5037.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
G. D. Snyder, U. M. Krishna, J. R. Falck, and A. A. Spector
Evidence for a membrane site of action for 14,15-EET on expression of aromatase in vascular smooth muscle
Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1936 - H1942.
[Abstract] [Full Text] [PDF]


Home page
Endocr. Rev.Home page
K. L. Chambliss and P. W. Shaul
Estrogen Modulation of Endothelial Nitric Oxide Synthase
Endocr. Rev., October 1, 2002; 23(5): 665 - 686.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
T. Ueyama, N. Shirasawa, M. Numazawa, K. Yamada, M. Shelangouski, T. Ito, and Y. Tsuruo
Gastric Parietal Cells: Potent Endocrine Role in Secreting Estrogen as a Possible Regulator of Gastro-Hepatic Axis
Endocrinology, August 1, 2002; 143(8): 3162 - 3170.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
R. Joannides, A. Costentin, M. Iacob, P. Compagnon, A. Lahary, and C. Thuillez
Influence of vascular dimension on gender difference in flow-dependent dilatation of peripheral conduit arteries
Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1262 - H1269.
[Abstract] [Full Text] [PDF]


Home page
J. Appl. Physiol.Home page
R. K. Dubey and E. K. Jackson
Genome and Hormones: Gender Differences in Physiology: Invited Review: Cardiovascular protective effects of 17{beta}-estradiol metabolites
J Appl Physiol, October 1, 2001; 91(4): 1868 - 1883.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
M. Zitzmann, M. Brune, B. Kornmann, J. Gromoll, S. von Eckardstein, A. von Eckardstein, and E. Nieschlag
The CAG Repeat Polymorphism in the AR Gene Affects High Density Lipoprotein Cholesterol and Arterial Vasoreactivity
J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4867 - 4873.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
R. K. Dubey and E. K. Jackson
Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms
Am J Physiol Renal Physiol, March 1, 2001; 280(3): F365 - F388.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
L. Nathan, W. Shi, H. Dinh, T. K. Mukherjee, X. Wang, A. J. Lusis, and G. Chaudhuri
Testosterone inhibits early atherogenesis by conversion to estradiol: Critical role of aromatase
PNAS, March 1, 2001; (2001) 51003698.
[Abstract] [Full Text]


Home page
J. Clin. Endocrinol. Metab.Home page
S. Worboys, D. Kotsopoulos, H. Teede, B. McGrath, and S. R. Davis
Evidence That Parenteral Testosterone Therapy May Improve Endothelium-Dependent and -Independent Vasodilation in Postmenopausal Women Already Receiving Estrogen
J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 158 - 161.
[Abstract] [Full Text]


Home page
EndocrinologyHome page
H. Sumitani, M. Shozu, T. Segawa, K. Murakami, H.-J. Yang, K. Shimada, and M. Inoue
In Situ Estrogen Synthesized by Aromatase P450 in Uterine Leiomyoma Cells Promotes Cell Growth Probably Via an Autocrine/Intracrine Mechanism
Endocrinology, October 1, 2000; 141(10): 3852 - 3861.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
L. Nathan, W. Shi, H. Dinh, T. K. Mukherjee, X. Wang, A. J. Lusis, and G. Chaudhuri
Testosterone inhibits early atherogenesis by conversion to estradiol: Critical role of aromatase
PNAS, March 13, 2001; 98(6): 3589 - 3593.
[Abstract] [Full Text] [PDF]