Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0264733 (ventricular dilatation)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been recently recognized that mammalian mitochondria contain most, if not all, of the components of fatty acid synthesis type II (FAS II). Among the components identified is 2-enoyl thioester reductase/mitochondrial enoyl-CoA reductase (Etr1/Mecr), which catalyzes the NADPH-dependent reduction of trans-2-enoyl thioesters, generating saturated acyl-groups. Although the FAS type II pathway is highly conserved, its physiological role in fatty acid synthesis, which apparently occurs simultaneously with breakdown of fatty acids in the same subcellular compartment in mammals, has remained an enigma. To study the in vivo function of the mitochondrial FAS in mammals, with special reference to Mecr, we generated mice overexpressing Mecr under control of the mouse metallothionein-1 promoter. These Mecr transgenic mice developed cardiac abnormalities as demonstrated by echocardiography in vivo, heart perfusion ex vivo, and electron microscopy in situ. Moreover, the Mecr transgenic mice showed decreased performance in endurance exercise testing. Our results showed a ventricular dilatation behind impaired heart function upon Mecr overexpression, concurrent with appearance of dysmorphic mitochondria. Furthermore, the data suggested that inappropriate expression of genes of FAS II can result in the development of hereditary cardiomyopathy.
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PMID:Myocardial overexpression of Mecr, a gene of mitochondrial FAS II leads to cardiac dysfunction in mouse. 1944 Mar 39

A heart under chronic stress undergoes cardiac remodelling, a process that comprises structural and functional changes including cardiomyocyte hypertrophy, interstitial fibrosis, contractile dysfunction, cell death and ventricular dilatation. Reactive oxygen species (ROS)-dependent modulation of intracellular signalling is implicated in the development of cardiac remodelling. Among the different ROS sources that are present in the heart, NADPH oxidases (NOXs) are particularly important in redox signalling. NOX isoforms are expressed in multiple cell types including cardiomyocytes, fibroblasts, endothelial cells and inflammatory cells-with the two main isoforms expressed in the heart being NOX2 and NOX4. Recent studies indicate that NOX-dependent signalling is involved in the development of cardiomyocyte hypertrophy, interstitial fibrosis and post-MI remodelling. NOXs may also be involved in the genesis of contractile dysfunction and myocyte apoptosis. Here, we review the main effects of NOXs in the pathogenesis of cardiac remodelling and the redox-sensitive signalling pathways that underlie these effects. The elucidation of mechanisms involved in NOX-dependent regulation of cardiac remodelling may lead to new therapeutic targets for heart failure.
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PMID:NADPH oxidases and cardiac remodelling. 2065 17

Oxidative stress plays an important role in the development of heart failure. Reactive oxygen and nitrogen species can be generated in all cell types that can be found in the myocardium. Potential sources of reactive oxygen species are the NADPH oxidases, nitric oxide synthase, lipoxygenases, cyclooxygenase, xanthine oxidase, cytochrome P450 enzymes, and the mitochondrial respiratory chain. The reactive oxygen species mediated damages are implicated in both the vascular system (endothelial dysfunction, atherosclerosis) and the myocardium (remodeling). Oixidative stress causes lipid and protein oixidation as well as single stranded DNA breaks and induces changes in signaling pathways which serve as central transducers of cardiac hypertrophic growth, remodeling and/or ventricular dilatation.
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PMID:[The role of oxidative stress in heart failure]. 2656 7