Immunohistological Localization and Possible Functions of Adrenomedullin

Marutsuka, Kousuke; Hatakeyama, Kinta; Sato, Yuichiro; Yamashita, Atsushi; Sumiyoshi, Akinobu; Asada, Yujiro

doi:10.1291/hypres.26.s33

Cited by 41 publications

(42 citation statements)

References 60 publications

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“…43,44 Immunoreactivity for AM was reported to be detected in SMCs of the intima and media of human atherosclerotic lesions. 40 Interestingly, its expression in coronary artery plaques obtained by directional atherectomy was augmented in patients with unstable angina in comparison with stable angina. 45 This finding is consistent with cell culture studies showing that AM production and secretion from cultured vascular SMCs were increased by factors, presumably proatherogenic, such as angiotensin II, endothelin-1, aldosterone, interleukin-1␤ (IL-1␤), and tumor necrosis factor-␣ (TNF-␣).…”

Section: Am Production In Blood Vessels and Atherosclerotic Lesionsmentioning

confidence: 98%

“…[37][38][39] According to Marutsuka et al, AM peptide was expressed in the endothelium of rat aortic arch in a site-dependent fashion, ie, intense immunohistochemical staining for AM was observed in the area where branches begin and on the inner side of the curvature. 40 In these areas, shear stress is relatively low, and indeed, production of AM has been found to be modulated by shear stress in cultured vascular endothelial cells. 41,42 Other factors shown to stimulate production of AM in endothelial cells are oxidative stress and hypoxia.…”

Section: Am Production In Blood Vessels and Atherosclerotic Lesionsmentioning

confidence: 99%

“…1 Production of AM was detected in macrophages not only in a cell culture experiment, 48 but also by immunohistochemical analysis where intense positive staining was found in advanced atherosclerotic vascular lesion of humans. 40 …”

Section: Am Production In Blood Vessels and Atherosclerotic Lesionsmentioning

confidence: 99%

“…Because of active production of AM in cultured vascular cells and vessel walls, AM has been assumed to act in a autocrine or paracrine fashion. 3,4,[37][38][39][40] Indeed, blockade of the actions of endogenous AM with anti-AM antibody or the AM antagonists impaired the vascular protective effects in vitro. 61,62 Meanwhile, according to our experiments in vivo, 63,64 the long-term infusion of AM significantly suppressed neointimal formation and adventitial hyperplasia, raising plasma AM levels by 1 to 2 fmol/mL, an increase within the physiological range.…”

Section: Plasma Level Of Am In Arteriosclerosismentioning

confidence: 99%

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Adrenomedullin

Kato

Tsuruda

Kita

et al. 2005

ATVB

145

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Abstract-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. Key Words: adrenomedullin Ⅲ vasodilatation Ⅲ endothelium Ⅲ smooth muscle cell Ⅲ arteriosclerosis C ardiovascular diseases secondary to arteriosclerosis of blood vessels are currently among the leading causes of death in developed countries. A number of factors, both humoral and mechanical, have been shown to modulate vascular function in humans as well as in experimental animals. 1 Blood vessel dysfunction resulting from an imbalance of those factors accelerates the process of vascular remodeling and atherosclerosis. 1 Vasoconstrictors including angiotensin II and endothelins not always but mostly act as proatherogenic factors, whereas vasodilators, either peptides or non-peptides, such as natriuretic peptides, nitric oxide (NO), and prostaglandin (PG) I 2 , have antiatherogenic properties. 1 In 1993, a new vasodilator peptide, adrenomedullin (AM), was isolated from the tissue extract of a human pheochromocytoma by monitoring cAMP levels in rat platelets. 2 Substantial levels of the AM peptide and gene expression were detected in the cardiovascular tissues including blood vessels. As listed in the Table, AM was found to exert a wide range of biological actions related to vascular functions in cultured cells, with which observations in vivo have been mostly accordant. Ever since the discovery of AM, efforts have been made to clarify the role of this bioactive peptide in blood vessels and a substantial amount of basic and clinical data has been accumulated. In this review, after summarizing the biochemical and pharmacological features of AM, we discuss its role in blood vessels, which is assumed to be protective, or inhibitory against the progression of vascular damage and remodeling. Biochemistry of AMHuman AM is a 52-aa peptide with a ring structure formed by a disulfide bond and amidated tyrosine at the C terminus ( Figure 1), both essential for binding to receptors and biological activity. 2-4 Based on sequence homology, AM is thought to belong to the calcitonin gene-related peptide (CGRP) superfamily. [2][3][4] Cloning of the cDNA encoding AM revealed the AM precursor peptide preproAM to comprise 185 amino acids, with the C terminus followed by a pair of basic amino acids, Arg-Arg, a typical processing signal (...

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Section: Am Production In Blood Vessels and Atherosclerotic Lesionsmentioning

confidence: 98%

Section: Am Production In Blood Vessels and Atherosclerotic Lesionsmentioning

confidence: 99%

Section: Am Production In Blood Vessels and Atherosclerotic Lesionsmentioning

confidence: 99%

Section: Plasma Level Of Am In Arteriosclerosismentioning

confidence: 99%

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Adrenomedullin

Kato

Tsuruda

Kita

et al. 2005

ATVB

145

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show abstract

“…4 Morphologically, dense manifestation of AM has been detected in macrophages within plaques of atherosclerotic lesions. 5 Shinomiya et al 6 reported an association between plasma AM concentration and carotid atherosclerosis in patients with stroke. Furthermore, we previously reported a relationship between plasma AM levels and pulse wave velocity (PWV), an indicator of arterial stiffness, in patients.…”

Section: Introductionmentioning

confidence: 99%

Hemodynamic and hormonal effects of exogenous adrenomedullin administration in humans and relationship to insulin resistance

2010

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Although adrenomedullin (AM) is a potent hypotensive peptide that acts mainly as a vasodilative and proliferation inhibitory factor, there have been few hemodynamic studies on AM in humans, especially concerning arterial stiffness and hormonal effects. In addition, AM is a suppressive factor in insulin resistance, suggesting that the effects of AM in a state of insulin resistance are important. To evaluate the effects of AM in humans, 28 participants were intravenously administered AM (5 pmol min À1 kg À1 ) for 90 min. They also received a representative vasodilator drug, nicardipine, as a reference drug. Blood pressure, heart rate, pulse wave velocity (PWV) and blood flow were monitored throughout the experiment. Hormonal changes were also monitored by blood tests. The effects of AM were compared with those of nicardipine. In addition, the effects of AM were re-evaluated against insulin resistance state. AM and nicardipine produced the same level of hypotension, but AM showed a more potent ability to increase heart rate, blood flow and cardiac output and reduce PWV. AM and nicardipine similarly stimulated plasma noradrenaline and renin activity. However, in the state of insulin resistance, favorable effects of AM on aortic stiffness were blunted and differences between AM and nicardipine disappeared. Furthermore, there was a significant correlation between maximum changes in the PWV induced by AM and the homeostasis model assessment of insulin resistance index (r¼0.58, P¼0.001). Our results suggest that AM may improve arterial stiffness and act as a compensatory factor against arterial sclerosis. Moreover, decreased reactivity of AM may participate in the progression of arterial sclerosis in insulin resistance.

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Adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin‐4 expression in the colonic epithelium

et al. 2023

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Adrenomedullin (AM) is a peptide with pleiotropic physiological functions that attenuates intestinal mucosal inflammation. However, the mechanism underpinning mucosal protection by AM is not fully understood, and its effect on intestinal epithelial cells remains unclear. Here, we investigated the effects of AM on junctional molecules in primary‐cultured murine intestinal epithelial cells and discovered that AM upregulates claudin‐4 expression. In a mouse model of dextran sulfate sodium‐induced colitis, AM administration also enhanced claudin‐4 expression and accelerated mucosal regeneration. Furthermore, AM reversed TNFα‐mediated downregulation of claudin‐4 and loss of cell–cell adhesion of the HCT116 human intestinal epithelial cell line in vitro. These results indicate that AM may enhance intestinal epithelial integrity by upregulating claudin‐4 expression.

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Immunohistological Localization and Possible Functions of Adrenomedullin

Cited by 41 publications

References 60 publications

Adrenomedullin

Adrenomedullin

Hemodynamic and hormonal effects of exogenous adrenomedullin administration in humans and relationship to insulin resistance

Adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin‐4 expression in the colonic epithelium

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