Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 38-yr-old man with external ophthalmoplegia, cardiac conduction abnormalities, hearing loss, and ragged-red fibres in skeletal muscle biopsy, developed severe signs of cardiac failure within a few months. Echocardiography and angiography demonstrated a dilated cardiomyopathy. Ubiquinone 140 mg day-1 did not stop the worsening of the cardiac status and cardiac transplantation was performed. Molecular analysis showed a heteroplasmic 4.5 kb mitochondrial DNA deletion in endomyocardial tissue. Eighteen months later, cardiac evolution is good and neurological status is stable.
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PMID:Cardiac transplantation in an incomplete Kearns-Sayre syndrome with mitochondrial DNA deletion. 818 12

A defective myocardial energy supply--due to lack of substrates and/or essential cofactors and a poor utilization efficiency of oxygen--may be a common final pathway in the progression of myocardial diseases of various etiologies. The vitamin-like essential substance coenzyme Q10, or ubiquinone, is a natural antioxidant and has a key role in oxidative phosphorylation. A biochemical rationale for using coenzyme Q10 as a therapy in heart disease was established years ago by Folkers and associates; however, this has been further strengthened by investigations of viable myocardial tissue from the author's series of 45 patients with various cardiomyopathies. Myocardial tissue levels of coenzyme Q10 determined by high-performance lipid chromatography were found to be significantly lower in patients with more advanced heart failure compared with those in the milder stages of heart failure. Furthermore, the myocardial tissue coenzyme Q10 deficiency might be restored significantly by oral supplementation in selected cases. In the author's open clinical protocol study with coenzyme Q10 therapy (100 mg daily) nearly two-thirds of patients revealed clinical improvement, most pronounced in those with dilated cardiomyopathy. Double-blind placebo-controlled trials have definitely confirmed that coenzyme Q10 has a place as adjunctive treatment in heart failure with beneficial effects on the clinical outcome, the patients' physical activity, and their quality of life. The positive results have been above and beyond the clinical status obtained from treatment with traditional principles--including angiotensin-converting enzyme inhibitors.
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PMID:Perspectives on therapy of cardiovascular diseases with coenzyme Q10 (ubiquinone). 824 94

The pathophysiological basis for the use of metabolic therapy in the treatment of heart failure is analyzed. Bioenergetical processes related to ATP bioavailability play a central role in regulating myocardial contractility at rest and on effort. Furthermore, a significant correlation has been demonstrated in diseased heart between ATP content, revealed at endomyocardial biopsy, and systolic and diastolic left ventricular indexes evaluated with invasive and noninvasive methods. Several international investigations demonstrate the beneficial effects of ubiquinone (coenzyme Q10) in the treatment of heart failure. Here the results of a study are reported that was conducted on patients with heart failure treated with ubiquinone. After 7 months of oral drug administration (100 mg/day), a significant improvement was observed in echocardiographic indexes of systolic function, cardiothoracic ratio, and clinical signs and symptoms of congestive heart failure. In conclusion, the introduction of metabolic drugs, such as ubiquinone, in the treatment of heart failure opens new horizons in the therapeutic approach to an ailment that entails substantial human and social costs.
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PMID:Role of metabolic therapy in cardiovascular disease. 824 95

Seven (7) males with effort angina and listed for coronary by-pass surgery had muscle biopsies taken from their vastus lateralis muscle for determination of muscle fiber types (%ST), ubiquinone (vitamin Q, UQ), oxidative and fermentative enzyme activities. Graded cycle ergometer exercise to determine intensities corresponding to onset of blood lactate accumulation set to 2.0 mmol x l-1 (WOBLA) and symptom limited exercise ('maximal', WSL) were also undertaken. WOBLA was positively related to %ST (r = 0.92, p < 0.001). %ST was on the other hand inversely related to UQ (r = -0.82, p < 0.05), the heart specific LD subunit LD-H (r = -0.96, p < 0.001), the isozyme LD3 as the fraction of LD (%LD3) (r = -0.93, p < 0.01), and the CK isozyme CKMB as the fraction of CK (%CKMB) (r = -0.88, p < 0.05). It was suggested that muscle UQ depletion in the patients was related to molecular oxygen and free oxygen radical formation. The lack of antioxidants then caused a radical trauma specifically to the ST fiber and their mitochondria. This could be a cause and-effect explanation for the selective ST fiber downregulation in effort angina and heart failure in general.
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PMID:Muscle ubiquinone in male effort angina patients. 909 75

RXRalpha null mutant mice display ocular and cardiac malformations, liver developmental delay, and die from cardiac failure around embryonic day (E) 14.5 pc. To dissect the molecular basis of the RXRalpha-associated cardiomyopathy, we performed subtractive hybridization and systematically characterized putative downstream target genes that were selectively lacking in the mutant embryos, both at early (E10.5) and late (E13.5) stages of mouse embryonic development. Approximately 50% of the subtracted clones (61/115) encoded proteins involved in intermediary metabolism and electron transport, suggesting an energy deficiency in the RXRalpha-/- embryos. In particular, clone G1, which encodes subunit 14.5b of the NADH-ubiquinone dehydrogenase complex, displayed a dose-dependent expression in the wild-type, heterozygous and RXRalpha mutant mice. This gene was also downregulated in a retinoid-deficient rat embryo model. ATP content and medium Acyl-CoA dehydrogenase mRNA were lower in RXRalpha mutant hearts compared to wild-type mice. Ultrastructural studies showed that the density of mitochondria per myocyte was higher in the RXRalpha mutant compared to wild-type littermates. We propose a model whereby defects in intermediary metabolism may be a causative factor of the RXRalpha-/- phenotype and resembles an embryonic form of dilated cardiomyopathy.
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PMID:Energy deprivation and a deficiency in downstream metabolic target genes during the onset of embryonic heart failure in RXRalpha-/- embryos. 942 47

Coenzyme Q (CoQ), a lipophilic substituted benzoquinone, is present in all animal and plant cells. It is endogenously synthesised in tissues and involved in a variety of cellular processes. It is well documented that CoQ is an obligatory component of the respiratory chain in the inner mitochondrial membrane coupled to ATP synthesis. However, its additional localisation in different subcellular fractions is probably associated with its multiple functions in the cell (as a part of extramitochondrial electron transport chains, a powerful antioxidant agent or a membrane stabiliser). The actions outlined for CoQ can explain its broad range of therapeutic effects. This presentation is a brief review of recent knowledge concerning medical aspects of CoQ in mammals. The energetic role seems sufficient to explain at least some of the clinical effects (heart failure, neurodegenerative diseases) but in other cases the antioxidant function may be a more convenient explanation. Nevertheless, a better knowledge of CoQ functions at the molecular level and additional well-designed studies are required to provide specific recommendation and definitive evidence of its therapeutic effects.
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PMID:[Coenzyme Q and its therapeutic use]. 1128 94

There are a number of theoretical reasons as to why 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) should be prescribed to patients with chronic heart failure (CHF). These agents are proven to prevent coronary heart disease, the major etiological factor in the development of CHF. Potential additional effects of these agents include inhibition of proinflammatory cytokine activity and other potential beneficial effects on cardiac remodeling. However, there are also possible adverse effects of this strategy, supported by the overriding observation that low plasma lipid levels portend a poorer prognosis in patients with established CHF. Potential mechanisms by which statins may directly confer adverse effects include a reduction in levels of the antioxidant ubiquinone and an increase in blood endotoxin levels, both of which may contribute to CHF disease progression. Given these uncertainties, an answer to the question of whether or not therapy for CHF should include statins requires a definitive clinical trial. The importance of such a trial is further highlighted by the already commonplace usage of statins amongst patients with CHF.
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PMID:Should patients with chronic heart failure be treated with "statins"? 1263 77

Although not currently indicated for chronic heart failure (CHF), statins have been associated with improved outcome in retrospective analysis. However, statin therapy reduces plasma levels of coenzyme Q(10) (ubiquinone), which may have adverse effects on heart failure states. We hypothesized that atorvastatin treatment improves endothelial function in patients with chronic heart failure independent of LDL-cholesterol alterations. Furthermore, we assessed how reductions in coenzyme Q(10) levels impact on potentially improved endothelial function. Twenty-four patients with stable, symptomatic heart failure (New York Heart Association Class II or III) and a left ventricular ejection fraction <40% were randomised to 40 mg atorvastatin or placebo for 6 weeks and crossed over to the other treatment arm for a further 6 weeks, after a 2-week wash out. Forearm resistance vessel function was assessed by venous occlusion plethysmography during infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and N(G)-monomethyl-L-arginine (L-NMMA) into the brachial artery. Atorvastatin treatment lowered triglycerides, LDL-cholesterol and coenzyme Q(10) levels (all p<0.001) and improved endothelium-dependent vasodilatation during acetylcholine infusion (p=0.015). Endothelium-dependent forearm blood flow improvements correlated with reductions in coenzyme Q(10) levels (p=0.011), but not with LDL-cholesterol levels (p=0.084). Coenzyme Q(10) remained the significant variable predicting improvement in NO dependent endothelial function after adjusting for LDL-cholesterol levels (p=0.041). In conclusion, short-term atorvastatin therapy improved endothelial function in chronic heart failure patients. Further studies are required to determine whether coenzyme Q(10) reductions are limiting the maximum favourable effects of statin therapy on the microcirculation.
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PMID:Endothelium-ameliorating effects of statin therapy and coenzyme Q10 reductions in chronic heart failure. 1572 Oct 28

Metabolic therapy involves the administration of a substance normally found in the body to enhance a metabolic reaction within the cell. This may be achieved in two ways. First, for some systems, a substance can be given to achieve greater than normal levels in the body so as to drive an enzymic reaction in a preferred direction. Second, metabolic therapy may be used to correct an absolute or relative deficiency of a cellular component. Thus, metabolic therapy differs greatly from most standard cardiovascular pharmacologic therapy such as the use of ACE Inhibitors b-blockers, statins and calcium channel antagonists that are given to block rather than enhance cellular processes. In this review we highlight some metabolic substances that have potential benefit in treating heart disease or improving outcomes after cardiovascular interventions. Glucose-insulin-potassium therapy is protective against myocardial ischaemia by elevating myocardial glycogen levels. Coenzyme Q(10) is a lipid-soluble antioxidant that plays a crucial role in cellular ATP production. Magnesium orotate, a key intermediate in the biosynthetic pathway of glycogen, has been shown to improve the energy status of the cell and improve recovery from cardioplegic arrest. The amino acid aspartate plays an important role in providing energy substrates for oxidative phosphorylation in the myocyte. By improving cellular energy production, metabolic therapy has the potential to benefit cardiac function during the stress of cardiac surgery, myocardial infarction and cardiac failure.
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PMID:The principles of metabolic therapy for heart disease. 1635 48

Statins, the most widely prescribed medications in patients with hyperlipidemia and coronary heart disease, have a number of pleiotropic actions beyond cholesterol lowering. They improve endothelial function, they have antioxidant and anti-inflammatory effects, they regulate neovascularization and have immunomodulatory activities. Experimental evidence suggests that statins may be beneficial in heart failure as they can inhibit myocardial hypertrophy, reduce cardiomyocyte loss by apoptosis, reduce oxidative stress and restore neurohormonal imbalance. Furthermore small randomised clinical trials showed that short term statin administration may improve key pathophysiological aspects of this syndrome. Finally retrospective analyses of large statin trials imply a long term profit on clinical outcome in this group of patients. These results however need to be reviewed with caution as certain studies have demonstrated that low serum cholesterol is associated with worse prognosis in HF and that ubiquinone levels, a micronutrient with antioxidant actions, reduces significantly following statin administration. Large prospective randomised controlled trials are needed to confirm the beneficial effect of statins on cardiovascular outcome in HF patients and further elucidate the contributing mechanisms. Finally the statin dose and the interaction with co-administered drugs need to be studied.
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PMID:Statins in heart failure. Beyond the lipid lowering effect. 1717 40


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