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(Circulation Research. 2006;99:234.)
© 2006 American Heart Association, Inc.

Editorials

Does 2-Methoxyestradiol Represent the New and Improved Hormone Replacement Therapy for Atherosclerosis?

Ana Paula V. Dantas, Kathryn Sandberg

From the Center for the Study of Sex Differences in Health, Aging and Disease, Georgetown University, Washington, DC.

Correspondence to Kathryn Sandberg, PhD, Director, Center for the Study of Sex Differences in Health, Aging and Disease, Georgetown University, Ste 232 Bldg D, 4000 Reservoir Rd NW, Washington, DC 20057. E-mail sandberg@georgetown.edu

See related article, pages 266–274

Key Words: hormone replacement therapy • estrogen metabolites • atherosclerosis • VSMC growth

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Much data from animal research¹ and clinical studies^2–4 indicate that estrogen can slow the development of atherosclerosis by inhibiting atherogenesis. Treatment with 17ß-estradiol (E₂) markedly inhibits the initiation and progression of coronary atherosclerotic plaques in several animal models of atherosclerosis.¹ These studies have not only established the atheroprotective effects of E₂ but have also shed light on the mechanisms of atheroprotection. Estrogen lowers major risk factors for developing atheroma plaques, such as lowering the risk for developing hypercholesterolemia. Initiation of the atherogenic response is promoted by hypercholesterolemia because chronic high levels of cholesterol in the bloodstream lead to prolonged retention of low-density lipoproteins in the subendothelial space.^4,5

The renin–angiotensin system (RAS) modulates several components of atherosclerotic process, including inflammation, oxidative stress, and hypertrophy of the vascular wall,⁶ and estrogen modulates most of, if not all, the components of the RAS cascade, including the synthesis of angiotensin II (Ang II), the key mediator of the RAS, and the 2 receptor subtypes (AT₁ and AT₂) that mediate Ang II action. Both animal⁷ and clinical studies⁸ demonstrate that estrogen inhibits angiotensin-converting enzyme activity, resulting in decreased levels of Ang II in the circulation and in specific tissues, including the aorta. Furthermore, E₂ reduces the membrane density of AT₁ receptors in many Ang II target tissues, including the vasculature,⁹ which is the same receptor that is targeted clinically to inhibit the progression of atherosclerosis through the use of AT₁ receptor antagonists.

The NO system is another signaling pathway that is regulated by . . . [Full Text of this Article]

Related Article:

2-Methoxyestradiol, an Estradiol Metabolite, Inhibits Neointima Formation and Smooth Muscle Cell Growth via Double Blockade of the Cell Cycle

Federica Barchiesi, Edwin K. Jackson, Juergen Fingerle, Delbert G. Gillespie, Bernhard Odermatt, and Raghvendra K. Dubey
Circ. Res. 2006 99: 266-274. [Abstract] [Full Text] [PDF]

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