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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2480.)
© 2005 American Heart Association, Inc.

Brief Reviews

Adrenomedullin

A Protective Factor for Blood Vessels

Johji Kato; Toshihiro Tsuruda; Toshihiro Kita; Kazuo Kitamura; Tanenao Eto

From the First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Japan

Correspondence to Johji Kato, MD, PhD, First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. E-mail jkjpn{at}med.miyazaki-u.ac.jp

Adrenomedullin (AM) is a vasodilator peptide having a wide range of biological actions such as reduction of oxidative stress and inhibition of endothelial cell apoptosis. The AM gene is expressed in vascular walls, and AM was found to be secreted from cultured vascular endothelial cells, smooth muscle cells, and adventitial fibroblasts. Plasma AM levels in patients with arteriosclerotic vascular diseases are elevated in possible association with the severity of the disease. When administered over a relatively short period, AM dilates blood vessels via an endothelium-dependent or independent mechanism. Experiments in vitro have shown that AM exerts multiple actions on cultured vascular cells, which are mostly protective or inhibitory against vascular damage and progression of arteriosclerosis. Either prolonged infusion or overexpression of AM suppressed intimal thickening, fatty streak formation, and perivascular hyperplasia in rodent models for vascular remodeling or atherosclerosis. Intimal thickening induced by periarterial cuff was more severe in AM gene-knockout mice than their littermates, suggesting a protective role for endogenous AM. Moreover, AM has recently been suggested to possess angiogenetic properties. Collectively, a body of evidence suggests that AM participates in the mechanism against progression of vascular damage and remodeling, thereby alleviating the ischemia of tissues and organs.

The vasodilator peptide adrenomedullin exerts various vascular actions, and its gene is expressed in three layers of the vascular wall. Both pharmacological and gene-manipulation studies showed an inhibitory effect of adrenomedullin on intimal thickening and perivascular hyperplasia, suggesting a possible role in inhibiting the progression of vascular damage and remodeling.

Key Words: adrenomedullin • vasodilatation • endothelium • smooth muscle cell • arteriosclerosis

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