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WDR12, a Member of ...
WDR12, a Member of Nucleolar PeBoW-Complex, Is Up-Regulated in Failing Hearts and Causes Deterioration of Cardiac Function
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Moilanen, A. M. (author)
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Rysa, J. (author)
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Kaikkonen, L. (author)
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Karvonen, T. (author)
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Mustonen, E. (author)
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Serpi, R. (author)
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Szabo, Z. (author)
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Tenhunen, O. (author)
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Bagyura, Z. (author)
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Napankangas, J. (author)
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Ohukainen, P. (author)
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Tavi, P. (author)
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Kerkela, R. (author)
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- Leosdottir, Margrét (author)
- Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups
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- Wahlstrand, Björn, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine
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- Hedner, Thomas, 1949 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine
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- Melander, Olle (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
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Ruskoaho, H. (author)
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(creator_code:org_t)
- 2015-04-27
- 2015
- English.
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
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Abstract
Subject headings
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- Aims In a recent genome-wide association study, WD-repeat domain 12 (WDR12) was associated with early-onset myocardial infarction (MI). However, the function of WDR12 in the heart is unknown. We characterized cardiac expression of WDR12, used adenovirus-mediated WDR12 gene delivery to examine effects of WDR12 on left ventricular (LV) remodeling, and analyzed relationship between MI associated WDR12 allele and cardiac function in human subjects. LV WDR12 protein levels were increased in patients with dilated cardiomyopathy and rats post-infarction. In normal adult rat hearts, WDR12 gene delivery into the anterior wall of the LV decreased interventricular septum diastolic and systolic thickness and increased the diastolic and systolic diameters of the LV. Moreover, LV ejection fraction (9.1%, P<0.05) and fractional shortening (12.2%, P<0.05) were declined. The adverse effects of WDR12 gene delivery on cardiac function were associated with decreased cellular proliferation, activation of p38 mitogen-activated protein kinase (MAPK)/heat shock protein (HSP) 27 pathway, and increased protein levels of Block of proliferation 1 (BOP1), essential for ribosome biogenesis. Post-infarction WDR12 gene delivery decreased E/A ratio (32%, P<0.05) suggesting worsening of diastolic function. In human subjects, MI associated WDR12 allele was associated significantly with diastolic dysfunction and left atrial size. WDR12 triggers distinct deterioration of cardiac function in adult rat heart and the MI associated WDR12 variant is associated with diastolic dysfunction in human subjects.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Annan klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Other Clinical Medicine (hsv//eng)
Keyword
- ACTIVATED PROTEIN-KINASE
- PEPTIDE GENE-EXPRESSION
- II-INDUCED
- HYPERTENSION
- SOCIETY-OF-CARDIOLOGY
- NATRIURETIC-PEPTIDE
- IMMUNE-RESPONSES
- WD-REPEAT
- IN-VIVO
- MYOCARDIAL-INFARCTION
- RIBOSOME
- BIOGENESIS
- Multidisciplinary Sciences
Publication and Content Type
- ref (subject category)
- art (subject category)
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Plos One
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- By the author/editor
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Moilanen, A. M.
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Rysa, J.
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Kaikkonen, L.
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Karvonen, T.
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Mustonen, E.
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Serpi, R.
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show more...
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Szabo, Z.
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Tenhunen, O.
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Bagyura, Z.
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Napankangas, J.
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Ohukainen, P.
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Tavi, P.
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Kerkela, R.
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Leosdottir, Marg ...
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Wahlstrand, Björ ...
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Hedner, Thomas, ...
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Melander, Olle
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Ruskoaho, H.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Other Clinical M ...
- Articles in the publication
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Plos One
- By the university
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University of Gothenburg
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Lund University