Adrenomedullin: molecular mechanisms and its role in cardiac disease.
Adrenomedullin (AM) is a potent, long-lasting vasoactive peptide originally isolated from human pheochromocytoma. Since its discovery, serum and tissue AM expression have been shown to be increased in experimental models and in patients with cardiac hypertrophy, myocardial infarction and end-stage heart failure with several beneficial effects. Considerable evidence exists for a wide range of autocrine, paracrine and endocrine mechanisms for AM which include vasodilatory, anti-apoptotic, angiogenic, anti-fibrotic, natriuretic, diuretic and positive inotropic. Thus, through regulation of body fluid or direct cardiac mechanisms, AM has additive and beneficial effects in the context of heart disease. Notable molecular mechanisms of AM include cyclic adenosine monophosphate, guanosine-3',5'-monophosphate, PI3K/Akt and MAPK-ERK-mediated cascades. Given the endogenous and multifunctional nature of AM, we consider this molecule to have great potential in the treatment of cardiovascular diseases. In agreement, early experimental and preliminary clinical studies suggest that AM is a new and promising therapy for cardiovascular diseases.
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Osaka, Japan.
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Yanagawa
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Nagaya
D053607:Adrenomedullin / Q000378:metabolism* / Q000627:therapeutic use; D000818:Animals; D002316:Cardiotonic Agents / Q000378:metabolism* / Q000627:therapeutic use; D002450:Cell Communication / Q000187:drug effects; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006331:Heart Diseases / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D009711:Nucleotides / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D002316:Cardiotonic Agents; D009711:Nucleotides; D053607:Adrenomedullin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases