Adrenomedullin

Abstract

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 (...

Prognostic Significance of Adrenomedullin in Patients With Heart Failure and With Myocardial Infarction

“…less expression in patients with stable angina compared to unstable angina. ADM is significantly raised in acute myocardial infarction, and correlates with severity of AMI (38). ADM levels in acute myocardial infarction are independently associated with subacute left ventricular systolic dysfunction via ejection fraction measurements (29).…”

“…The receptors of ADM are a complex of receptor-activity modifying proteins (RAMP) and calcitonin receptor-like receptor (CRLR) (40). The mechanisms of action of ADM are thought so far to be through the generation of nitric oxide via nitric oxide-cyclic guanine monophosphate pathway or through increased intracellular cyclic adenosine monophosphate which activates protein kinase A which then activates nitric oxide synthase or through phosphatidylinositol kinase -3 activation and Akt phosphorylation resulting in enhanced stimulation of endothelial nitric oxide synthase (2,38).…”

Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: A review of experimental studies

“…However, adrenomedullin (ADM), another peptide from the calcitonin family, co-localizes with CGRP in some tissues, including perivascular nerves and dorsal root ganglia . ADM is invloved in angiogenesis (Ribatti et al, 2005) and endothelial protection (Kato et al, 2005). ADM also can produce vasodilation by binding CGRP-1 receptor, although its vasodilation effect is relatively weaker when compared to CGRP (Aiyar et al, 1996;McLatchie et al, 1998;Hagner et al, 2002).…”

“…Besides these two classic hypotheses, other mechanisms are also potentially involved in SCS effects. First, the release of vasodilators and other peptides may improve endothelial function (Yu et al, 2007) and supress the formation of new atherosclerotic plaques (Kato et al, 2005). The role of endothelial cells and their contribution to the vasodilation effect of SCS are still unclear.…”

Aldosterone antisecretagogue and antihypertensive actions of adrenomedullin in patients with primary aldosteronism

“…AM production is most likely stimulated in the vasculature, as a reaction to a variety of stress-related factors, including hormones, mechanical stresses, metabolic factors and cytokines. 34 In addition to inflammation, many kinds of stimuli to blood vessels would influence AM levels and consequently CRP. Although AM is merely one factor regulating CRP production, this intimate relationship of AM with CRP via IL-6 may represent a pivotal role for AM in a mechanism linking serum CRP and vascular alterations.…”