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Glycosylated Chromo...
Glycosylated Chromogranin A in Heart Failure : Implications for Processing and Cardiomyocyte Calcium Homeostasis
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Ottesen, Anett Hellebø (författare)
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Carlson, Cathrine R (författare)
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Louch, William E (författare)
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visa fler...
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Dahl, Mai Britt (författare)
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Sandbu, Ragnhild A (författare)
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Johansen, Rune Forstrøm (författare)
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Jarstadmarken, Hilde (författare)
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Bjørås, Magnar (författare)
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Høiseth, Arne Didrik (författare)
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Brynildsen, Jon (författare)
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Sjaastad, Ivar (författare)
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- Stridsberg, Mats (författare)
- Uppsala universitet,Biokemisk endokrinologi
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Omland, Torbjørn (författare)
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Christensen, Geir (författare)
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Røsjø, Helge (författare)
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(creator_code:org_t)
- 2017
- 2017
- Engelska.
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Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 10:2
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- BACKGROUND: Chromogranin A (CgA) levels have previously been found to predict mortality in heart failure (HF), but currently no information is available regarding CgA processing in HF and whether the CgA fragment catestatin (CST) may directly influence cardiomyocyte function.METHODS AND RESULTS: CgA processing was characterized in postinfarction HF mice and in patients with acute HF, and the functional role of CST was explored in experimental models. Myocardial biopsies from HF, but not sham-operated mice, demonstrated high molecular weight CgA bands. Deglycosylation treatment attenuated high molecular weight bands, induced a mobility shift, and increased shorter CgA fragments. Adjusting for established risk indices and biomarkers, circulating CgA levels were found to be associated with mortality in patients with acute HF, but not in patients with acute exacerbation of chronic obstructive pulmonary disease. Low CgA-to-CST conversion was also associated with increased mortality in acute HF, thus, supporting functional relevance of impaired CgA processing in cardiovascular disease. CST was identified as a direct inhibitor of CaMKIIδ (Ca(2+)/calmodulin-dependent protein kinase IIδ) activity, and CST reduced CaMKIIδ-dependent phosphorylation of phospholamban and the ryanodine receptor 2. In line with CaMKIIδ inhibition, CST reduced Ca(2+) spark and wave frequency, reduced Ca(2+) spark dimensions, increased sarcoplasmic reticulum Ca(2+) content, and augmented the magnitude and kinetics of cardiomyocyte Ca(2+) transients and contractions.CONCLUSIONS: CgA-to-CST conversion in HF is impaired because of hyperglycosylation, which is associated with clinical outcomes in acute HF. The mechanism for increased mortality may be dysregulated cardiomyocyte Ca(2+) handling because of reduced CaMKIIδ inhibition.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- Ca2+/calmodulin–dependent protein kinase II
- biomarker
- catestatin
- chromogranin A
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- Av författaren/redakt...
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Ottesen, Anett H ...
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Carlson, Cathrin ...
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Louch, William E
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Dahl, Mai Britt
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Sandbu, Ragnhild ...
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Johansen, Rune F ...
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visa fler...
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Jarstadmarken, H ...
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Bjørås, Magnar
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Høiseth, Arne Di ...
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Brynildsen, Jon
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Sjaastad, Ivar
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Stridsberg, Mats
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Omland, Torbjørn
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Christensen, Gei ...
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Røsjø, Helge
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visa färre...
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Circulation Hear ...
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