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The Early-Onset Myo...
The Early-Onset Myocardial Infarction Associated PHACTR1 Gene Regulates Skeletal and Cardiac Alpha-Actin Gene Expression
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Kelloniemi, A. (författare)
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Szabo, Z. (författare)
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Serpi, R. (författare)
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Napankangas, J. (författare)
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Ohukainen, P. (författare)
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Tenhunen, O. (författare)
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Kaikkonen, L. (författare)
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Koivisto, E. (författare)
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Bagyura, Z. (författare)
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Kerkela, R. (författare)
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- Leosdottir, Margrét (författare)
- Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups
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- Hedner, Thomas, 1949 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine
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- Melander, Olle (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
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Ruskoaho, H. (författare)
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Rysa, J. (författare)
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(creator_code:org_t)
- 2015-06-22
- 2015
- Engelska.
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:6
- Relaterad länk:
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https://doi.org/10.1...
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http://www.ncbi.nlm.... (free)
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http://dx.doi.org/10... (free)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- The phosphatase and actin regulator 1 (PHACTR1) locus is a very commonly identified hit in genome-wide association studies investigating coronary artery disease and myocardial infarction (MI). However, the function of PHACTR1 in the heart is still unknown. We characterized the mechanisms regulating Phactr1 expression in the heart, used adenoviral gene delivery to investigate the effects of Phactr1 on cardiac function, and analyzed the relationship between MI associated PHACTR1 allele and cardiac function in human subjects. Phactr1 mRNA and protein levels were markedly reduced (60%, P<0.01 and 90%, P<0.001, respectively) at 1 day after MI in rats. When the direct myocardial effects of Phactr1 were studied, the skeletal a-actin to cardiac a-actin isoform ratio was significantly higher (1.5-fold, P<0.05) at 3 days but 40% lower (P<0.05) at 2 weeks after adenovirus-mediated Phactr1 gene delivery into the anterior wall of the left ventricle. Similarly, the skeletal a-actin to cardiac a-actin ratio was lower at 2 weeks in infarcted hearts overexpressing Phactr1. In cultured neonatal cardiac myocytes, adenovirus-mediated Phactr1 overexpression for 48 hours markedly increased the skeletal a-actin to cardiac a-actin ratio, this being associated with an enhanced DNA binding activity of serum response factor. Phactr1 overexpression exerted no major effects on the expression of other cardiac genes or LV structure and function in normal and infarcted hearts during 2 weeks' follow-up period. In human subjects, MI associated PHACTR1 allele was not associated significantly with cardiac function (n = 1550). Phactr1 seems to regulate the skeletal to cardiac a-actin isoform ratio.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- CORONARY-ARTERY-DISEASE
- ACTIVATED PROTEIN-KINASE
- GENOME-WIDE
- ASSOCIATION
- HUMAN ENDOTHELIAL-CELLS
- NATRIURETIC-PEPTIDE
- SUSCEPTIBILITY LOCI
- HEART-FAILURE
- HYPERTROPHY
- DYNAMICS
- P38
- Multidisciplinary Sciences
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Plos One
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Till lärosätets databas
- Av författaren/redakt...
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Kelloniemi, A.
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Szabo, Z.
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Serpi, R.
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Napankangas, J.
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Ohukainen, P.
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Tenhunen, O.
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visa fler...
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Kaikkonen, L.
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Koivisto, E.
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Bagyura, Z.
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Kerkela, R.
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Leosdottir, Marg ...
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Hedner, Thomas, ...
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Melander, Olle
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Ruskoaho, H.
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Rysa, J.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
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Plos One
- Av lärosätet
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Göteborgs universitet
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Lunds universitet