Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenomedullin is a novel hypotensive peptide, newly discovered in pheochromocytoma. Because immunoreactive adrenomedullin is present in human plasma, adrenomedullin may play a role in regulating blood pressure. A recent report showed that human adrenomedullin mRNA is expressed not only in pheochromocytoma but also in the normal adrenal medulla, kidney, lung, and ventricle. However, whether or not these organs actually release adrenomedullin into the circulation remains unknown. To investigate the sites of production and degradation of adrenomedullin in human subjects, we obtained blood samples from various sites and measured immunoreactive adrenomedullin concentrations. In study 1, blood samples were obtained from the infrarenal inferior vena cava, suprarenal inferior vena cava, superior vena cava, right atrium, right ventricle, pulmonary artery, pulmonary capillary, left ventricle, and aorta during cardiac catheterization in 15 patients with ischemic heart disease (67 +/- 10 years). In study 2, blood samples were taken from the infrarenal inferior vena cava, suprarenal inferior vena cava, right and left renal veins, and left adrenal vein in 5 hypertensive patients (42 +/- 14 years) suspected of having renovascular hypertension. In study 3, peripheral venous blood samples were obtained in 2 patients (males, 45 and 36 years old) with pheochromocytoma at rest and during hypertensive attacks. Plasma adrenomedullin concentrations were measured by a newly developed radioimmunoassay. In study 1, there were no significant differences in plasma adrenomedullin concentrations in various sites of the right-side circulation. There was no step-up of plasma adrenomedullin levels in the coronary sinus. However, the plasma concentration of adrenomedullin in aorta was slightly but significantly lower than in pulmonary artery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical studies on the sites of production and clearance of circulating adrenomedullin in human subjects. 796 20

Adrenomedullin (AM), a potent vasodilator peptide originally isolated from pheochromocytoma, is expressed in cardiovascular tissues such as those of the cardiac atria and ventricles. Cell culture experiments have shown that AM peptide is synthesized and secreted from cardiac myocytes and fibroblasts of neonatal rats. Humoral factors, such as angiotensin II (Ang II) and endothelin-1 (ET-1), and mechanical stress due to pressure and volume overload to the heart have been shown to be involved in AM expression of the myocardium in both in vitro and in vivo studies. The effects of AM on cardiomyocytes and cardiac fibroblasts have been examined in in vitro studies, with the result that AM was shown to exert inhibitory actions on myocyte hypertrophy and on proliferation and collagen production of cardiac fibroblasts in an autocrine or paracrine manner. In rats, experimental therapeutic intervention consisting of transfer of the AM gene or of recombinant AM appears to partly inhibit the progression of cardiac hypertrophy and remodeling. It has been shown that the calcitonin receptor-like receptor (CRLR) and receptor-activity-modifying protein (RAMP) act together to function as AM receptors, although in this regard there are a number of issues, including the cellular mechanism of AM actions, that remain to be addressed. In addition, the role of proadrenomedullin N-terminal 20 peptide (PAMP), which is derived from preproAM, is another topic for future experiments. Collectively, the research data accumulating in this area suggest that AM plays a role as an autocrine or paracrine hormone in the cardiac ventricles, and that AM might be utilized as a therapeutic tool in the treatment of hypertensive or ischemic heart disease.
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PMID:Adrenomedullin: a possible autocrine or paracrine hormone in the cardiac ventricles. 1263 Aug 21

Adrenomedullin (AM) has been shown to protect against cardiac remodeling. In this study, we investigated the potential role of AM in myocardial ischemia-reperfusion (I/R) injury through adenovirus-mediated gene delivery. One week after AM gene delivery, rats were subjected to 30-min coronary occlusion, followed by 2-h reperfusion. AM gene transfer significantly reduced the ratio of infarct size to ischemic area at risk and the occurrence of sustained ventricular fibrillation compared with control rats. AM gene delivery also attenuated apoptosis, assessed by both terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and DNA laddering. The effect of AM gene transfer on infarct size, arrhythmia, and apoptosis was abolished by an AM antagonist, calcitonin gene-related peptide [CGRP(8-37)]. Expression of human AM significantly increased cardiac cGMP levels and reduced superoxide production, superoxide density, NAD(P)H oxidase activity, p38 MAPK activation, and Bax levels. Moreover, AM increased Akt and Bad phosphorylation and Bcl-2 levels, but decreased caspase-3 activation. These results indicate that AM protects against myocardial infarction, arrhythmia, and apoptosis in I/R injury via suppression of oxidative stress-induced Bax and p38 MAPK phosphorylation and activation of the Akt-Bad-Bcl-2 signaling pathway. Successful application of this technology may have a protective effect in coronary artery diseases.
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PMID:Adrenomedullin gene delivery attenuates myocardial infarction and apoptosis after ischemia and reperfusion. 1280 25

Adrenomedullin is a 52-amino acid peptide that was first isolated from human pheochromocytoma. Subsequently, it was found to be distributed widely in the body, including throughout the cardiovascular system. It belongs to a family of peptides that include calcitonin gene-related peptide and amylin. Adrenomedullin causes vasorelaxation and influences vascular proliferation and interacts closely with nitric oxide, and it may have a role in the pathophysiology of hypertension, ischemic heart disease, and cardiac and renal failure. Nonpeptide agonists or antagonists of adrenomedullin may have potential therapeutic application. The role of adrenomedullin in septicemic shock also merits further investigation.
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PMID:Adrenomedullin: its role in the cardiovascular system. 1547 33