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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:e135.)
© 2005 American Heart Association, Inc.

Letters to the Editor

Toll-Like Receptors, Endocrine Stress Response, and Arteriosclerosis

Stefan R. Bornstein

Department of Medicine, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Germany

Henning Morawietz

Division of Vascular Endothelium and Microcirculation, Department of Medicine Carl Gustav Carus, University of Technology Dresden, Germany

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

To the Editor:

There is increasing evidence that Toll-like receptor (TLR)-dependent signaling and cell activation is critically involved in the pathogenesis of arteriosclerosis.

The article by M. Kazemi et al impressively demonstrates that Toll-like receptor agonists induce lipid accumulation and proteins involved in atherosclerotic plaque development such as adipocyte fatty acid-binding protein (aP2) in macrophages.¹ Therefore there is a molecular link between TLR and foam cell formation.

While bacterial toxins activate macrophages through Toll-like receptor -2 and -4, noninfectious stimuli such as minimally oxidized LDL also use the same signaling pathways and will trigger a TLR-4–dependent proinflammatory response in macrophages.²

TLR may, however, not only be a "central gateway to the vessel wall"³ and mediate the local process of arteriosclerotic plaque formation but may also relate to systemic pathomechanism of arterial disease. The endocrine stress response, including the release of glucocorticoids and the activation of the renin–angiotensin aldosterone system, is clearly implicated in the process of endothelial dysfunction and arteriosclerosis both through the increase in blood pressure and direct effects on the endothelial cell wall.

We have recently demonstrated an important role for TLR-2 and TLR-4 in the adrenal stress response.^4,5 TLRs are expressed in adrenal cells, and TLR agonists stimulate the release of steroids from human adrenal cells.⁶ TLR-2–deficient mice have an impaired steroid release during endotoxemia.⁵

Consistent with the increased lipid accumulation and adipocyte fatty acid binding protein (aP2) expression induced by Toll-like receptor agonists described by M. Kazemi et al,¹ similarly mineralocorticoids and glucocorticoids are known to . . . [Full Text of this Article]

Mahmood R. Kazemi; Carl Grunfeld; Kenneth R. Feingold

Department of Medicine, Metabolism Section, University of California, San Francisco, Department of Veterans Affairs Medical Center, San Francisco, Calif