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)

We describe the changes in proportions of myofibrillar proteins elicited by chronic congestive heart failure in the costal diaphragm (DIA) of humans using one and two-dimensional electrophoretic techniques. Three myosin heavy chain (MHC) isoforms were found in the DIA from control subjects: slow MHC I (43 +/- S.E. 2%), fast MHC IIa (41 +/- 2%) and fast MHC IIb (17 +/- 1%). In heart failure DIA, the percentage of MHC I was increased to 57 +/- 2%, while that of MHC IIb was decreased to 8 +/- 2 (P < 0.001 for both cases). Similarly, this DIA had higher molar ratios (%) of the slow myosin light chain isoforms (i.e. 1sa, 1sb, and 2s), and lower molar ratios of the fast isoforms (i.e. 1f, 2f, and 3f) than control DIA. Heart failure DIA also contained lower proportions of both alpha-tropomyosin and fast isoforms of troponin-T, I and C than control DIA. These results indicate that heart failure elicits fast-to-slow transformations of both myosin and regulatory proteins of human costal DIA. These changes can be viewed as an increase in slow-twitch characteristics of the DIA and differ from the adaptations elicited by heart failure in limb muscles.
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PMID:Changes in myofibrillar protein composition of human diaphragm elicited by congestive heart failure. 900 69

Chronic heart failure is characterized by changes in skeletal muscle that contribute to exercise intolerance and muscle weakness. To determine whether changes in the quantity and isoform distribution of key myofibrillar proteins are related to altered gene expression, we measured skeletal muscle myofibrillar mRNA abundance in nine heart failure patients (mean +/- SE; 63 +/- 3 yr) and nine controls (70 +/- 3 yr). In addition, we assessed the relationship of circulating levels of anabolic and catabolic hormones, as well as local expression of insulin-like growth factor (IGF)-I, to myofibrillar mRNA abundance. Heart failure patients were characterized by lower abundance of mRNA encoding the myosin heavy chain (MHC) I isoform (P < 0.01), whereas MHC IIa and MHC IIx mRNA did not differ between groups. Actin mRNA was also lower in heart failure patients compared with controls (P < 0.001). The expression of each MHC isoform transcript correlated with its respective protein product (MHC I: r = 0.656, P < 0.01; MHC IIa: r = 0.489, P < 0.05; MHC IIx: r = 0.505, P < 0.05; n = 18 for all). In addition to changes in myofibrillar transcripts, we found lower (P < 0.01) skeletal muscle IGF-1Ea mRNA content in heart failure patients. Myofibrillar mRNA levels were positively associated with skeletal muscle IGF-1Ea transcript levels (range of r values: 0.663-0.765; P values: <0.01 to <0.001) and modestly associated with circulating markers of immune activation (range of r values: -0.487 to -0.555; P values: <0.05 to <0.03). Our findings suggest that alterations in skeletal muscle MHC content and isoform distribution in heart failure may derive, in part, from changes in MHC gene expression. The relationships of myofibrillar mRNA content to both local and circulating hormones further suggest that alterations in the balance between anabolic and catabolic hormones in heart failure patients may influence skeletal muscle myofibrillar protein phenotype by altering gene expression.
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PMID:Skeletal muscle myofibrillar mRNA expression in heart failure: relationship to local and circulating hormones. 1614 80

Diaphragm myopathy has been described in patients with heart failure (HF), with alterations in myosin heavy chains (MHC) expression. The pathways that regulate MHC expression during HF have not been described, and myogenic regulatory factors (MRFs) may be involved. The purpose of this investigation was to determine MRF mRNA expression levels in the diaphragm. Diaphragm muscle from both HF and control Wistar rats was studied when overt HF had developed, 22 days after monocrotaline administration. MyoD, myogenin and MRF4 gene expression were determined by RT-PCR and MHC isoforms by polyacrylamide gel electrophoresis. Heart failure animals presented decreased MHC IIa/IIx protein isoform and MyoD gene expression, without altering MHC I, IIb, myogenin and MRF4. Our results show that in HF, MyoD is selectively down-regulated, which might be associated with alterations in MHC IIa/IIx content. These changes are likely to contribute to the diaphragm myopathy caused by HF.
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PMID:Down-regulation of MyoD gene expression in rat diaphragm muscle with heart failure. 1846 74