Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Digitalis, diuretics and vasodilators are considered the standard therapy for patients with congestive heart failure, for which treatment is tailored according to the severity of the syndrome and the patient profile. Apart from the clinical seriousness, heart failure is always characterized by an energy depletion status, as indicated by low intramyocardial ATP and coenzyme Q10 levels. We investigated safety and clinical efficacy of Coenzyme Q10 (CoQ10) adjunctive treatment in congestive heart failure which had been diagnosed at least 6 months previously and treated with standard therapy. A total of 2664 patients in NYHA classes II and III were enrolled in this open noncomparative 3-month postmarketing study in 173 Italian centers. The daily dosage of CoQ10 was 50-150 mg orally, with the majority of patients (78%) receiving 100 mg/day. Clinical and laboratory parameters were evaluated at the entry into the study and on day 90; the assessment of clinical signs and symptoms was made using from two-to seven-point scales. The results show a low incidence of side effects: 38 adverse effects were reported in 36 patients (1.5%) of which 22 events were considered as correlated to the test treatment. After three months of test treatment the proportions of patients with improvement in clinical signs and symptoms were as follows: cyanosis 78.1%, oedema 78.6%, pulmonary rales 77.8%, enlargement of liver area 49.3%, jugular reflux 71.81%, dyspnoea 52.7%, palpitations 75.4%, sweating 79.8%, subjective arrhytmia 63.4%, insomnia 662.8%, vertigo 73.1% and nocturia 53.6%. Moreover we observed a contemporary improvement of at least three symptoms in 54% of patients; this could be interpreted as an index of improved quality of life.
Mol Aspects Med 1994
PMID:Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. 775 41

Cardiac remodeling, CR, is a complex and rather controversial issue and results from the, sometimes opposite, trophic effects of pure mechanical overload, and susceptibility factors, as senescence, aetiologies, as ischemia, and the neurohormonal reaction. The molecular mechanisms of CR are heritable and had, in the past, increased fitness, as such CR belongs to evolutionary medicine. Aldosterone production plays an important role in the remodeling of the heart. (i) There are numerous evidences that aldosterone induces fibrosis in all the cardiovascular system in the presence of high sodium diet. The aldosterone receptor is a transcriptional factor and the pathways that lead to aldosterone-induced fibrosis are multiple. Aldosterone induces the expression of the angiotensin II receptors subtype I and that of the glucocorticoid receptors. The RALES trial have recently evidenced a significant beneficial effect of spironolactone on both mortality and morbidity in heart failure, and a substudy has shown that these effects are linked to a reduction is fibrosis. (ii) An intracardiac production of aldosterone and corticosterone have been evidenced in the rat. Aldosterone production is regulated by low sodium/high potassium diets and by angiotensin II and is predominant in atria, cardiac production is low as compared to the adrenal production, nevertheless it results in high local concentrations, just like angiotensin II. In rats, myocardial infarction activates aldosterone production and this activation is prevented by losartan. Heart failure, in human, activates aldosterone production and is accompanied by a significant increase of the arteriovenous difference in aldosterone by the myocardium. To conclude (i) after a myocardial infarction local production of aldosterone and angiotensin II are likely to play a major role in regulating collagen turnover and fibrous tissue formation; (ii) during heart failure, the activation of adrenal and cardiovascular production of aldosterone belongs to the neurohormonal reaction and would play a detrimental role in producing reactive fibrosis.
J Mol Cell Cardiol 2002 Dec
PMID:Molecular mechanisms of myocardial remodeling. The role of aldosterone. 1250 56

This paper has a focus on the early history of aldosterone. The Taits take us on a chronological trawl through the history in which they had a first hand role and made a major contribution-their bioassay was in many ways the key. The gifted Swiss chemists made a critical contribution to the scale and isolation of larger amounts. This was international collaboration at its best. Developing technologies were utilised as crucial cutting edge applications in the advancing front, technology transfer before the word was invented. Measurement of aldosterone and angiotensin were crucial advances to the understanding of the regulation of the hormone. In the period 1960-2003, some 30,000 papers mentioned aldosterone as a keyword, even so advances on a larger scale were slow. I have indicated some of my own work with the Howard Florey team using the adrenal autotransplant in the conscious sheep. Recently, the understanding of the role of induced proteins, the flow on from the RALES trial and the development of eplerenone has revitalised the aldosterone field.
Mol Cell Endocrinol 2004 Mar 31
PMID:The discovery, isolation and identification of aldosterone: reflections on emerging regulation and function. 1513 95

For the past 50 years, the physiological action of aldosterone was considered to be on epithelial tissues to maintain fluid and electrolyte homeostasis. Recently, a nonepithelial, pathophysiologic, proinflammatory role for aldosterone has been inferred from studies on mineralocorticoid/salt administration, with or without mineralocorticoid receptor (MR) blockade, in experimental animals, and from clinical studies such as RALES and EPHESUS. More recently still, it has become clear that the pathophysiologic trigger for the vascular inflammatory response observed is not necessarily aldosterone per se, but inappropriate activation of vascular wall MR. MR can be inappropriately activated by aldosterone in the context of an inappropriate salt status, or by glucocorticoids in the context of tissue damage. The studies supporting this latter conclusion, and the novel mechanisms proposed to support this concept, are details in the text to follow.
Mol Cell Endocrinol 2004 Mar 31
PMID:Aldosterone, mineralocorticoid receptors and vascular inflammation. 1513 27

For 50 years aldosterone has been thought to act primarily on epithelia to regulate fluid and electrolyte homeostasis. Mineralocorticoid receptors (MR), however, are also expressed in nonepithelial tissues such as the heart and vascular smooth muscle. Recently pathophysiologic effects of nonepithelial MR activation by aldosterone have been demonstrated, in the context of inappropriate mineralocorticoid for salt status, including coronary vascular inflammation and cardiac fibrosis. Consistent with experimental studies, clinical trials (RALES, EPHESUS), have demonstrated a reduced mortality and morbidity when MR antagonists are included in the treatment of moderate-severe heart failure. The pathogenesis of MR-mediated cardiovascular disease is a complex, multifactorial process that involves loss of vascular reactivity, hypertension, inflammation of the vasculature and end organs (heart and kidney), oxidative stress and tissue fibrosis (cardiac and renal). This review will discuss the mechanisms by which MR, located in the various cell types that comprise the heart, plays a central role in the development of cardiomyocyte failure, tissue inflammation, remodelling and hypertension.
Mol Cell Endocrinol 2012 Mar 24
PMID:Mechanisms of mineralocorticoid salt-induced hypertension and cardiac fibrosis. 2193 Jan 86