The Early-Onset Myocardial Infarction Associated PHACTR1 Gene Regulates Skeletal and Cardiac Alpha-Actin Gene Expression.

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The Early-Onset Myocardial Infarction Associated PHACTR1 Gene Regulates Skeletal and Cardiac Alpha-Actin Gene Expression. / Kelloniemi, Annina; Szabo, Zoltan; Serpi, Raisa; Näpänkangas, Juha; Ohukainen, Pauli; Tenhunen, Olli; Kaikkonen, Leena; Koivisto, Elina; Bagyura, Zsolt; Kerkelä, Risto; Leosdottir, Margrét; Hedner, Thomas; Melander, Olle; Ruskoaho, Heikki; Rysä, Jaana.

I: PLoS ONE, Vol. 10, Nr. 6, e0130502, 2015.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Kelloniemi, A, Szabo, Z, Serpi, R, Näpänkangas, J, Ohukainen, P, Tenhunen, O, Kaikkonen, L, Koivisto, E, Bagyura, Z, Kerkelä, R, Leosdottir, M, Hedner, T, Melander, O, Ruskoaho, H & Rysä, J 2015, 'The Early-Onset Myocardial Infarction Associated PHACTR1 Gene Regulates Skeletal and Cardiac Alpha-Actin Gene Expression.', PLoS ONE, vol. 10, nr. 6, e0130502. https://doi.org/10.1371/journal.pone.0130502

APA

Kelloniemi, A., Szabo, Z., Serpi, R., Näpänkangas, J., Ohukainen, P., Tenhunen, O., Kaikkonen, L., Koivisto, E., Bagyura, Z., Kerkelä, R., Leosdottir, M., Hedner, T., Melander, O., Ruskoaho, H., & Rysä, J. (2015). The Early-Onset Myocardial Infarction Associated PHACTR1 Gene Regulates Skeletal and Cardiac Alpha-Actin Gene Expression. PLoS ONE, 10(6), [e0130502]. https://doi.org/10.1371/journal.pone.0130502

CBE

Kelloniemi A, Szabo Z, Serpi R, Näpänkangas J, Ohukainen P, Tenhunen O, Kaikkonen L, Koivisto E, Bagyura Z, Kerkelä R, Leosdottir M, Hedner T, Melander O, Ruskoaho H, Rysä J. 2015. The Early-Onset Myocardial Infarction Associated PHACTR1 Gene Regulates Skeletal and Cardiac Alpha-Actin Gene Expression. PLoS ONE. 10(6):Article e0130502. https://doi.org/10.1371/journal.pone.0130502

MLA

Vancouver

Author

Kelloniemi, Annina ; Szabo, Zoltan ; Serpi, Raisa ; Näpänkangas, Juha ; Ohukainen, Pauli ; Tenhunen, Olli ; Kaikkonen, Leena ; Koivisto, Elina ; Bagyura, Zsolt ; Kerkelä, Risto ; Leosdottir, Margrét ; Hedner, Thomas ; Melander, Olle ; Ruskoaho, Heikki ; Rysä, Jaana. / The Early-Onset Myocardial Infarction Associated PHACTR1 Gene Regulates Skeletal and Cardiac Alpha-Actin Gene Expression. I: PLoS ONE. 2015 ; Vol. 10, Nr. 6.

RIS

TY - JOUR

T1 - The Early-Onset Myocardial Infarction Associated PHACTR1 Gene Regulates Skeletal and Cardiac Alpha-Actin Gene Expression.

AU - Kelloniemi, Annina

AU - Szabo, Zoltan

AU - Serpi, Raisa

AU - Näpänkangas, Juha

AU - Ohukainen, Pauli

AU - Tenhunen, Olli

AU - Kaikkonen, Leena

AU - Koivisto, Elina

AU - Bagyura, Zsolt

AU - Kerkelä, Risto

AU - Leosdottir, Margrét

AU - Hedner, Thomas

AU - Melander, Olle

AU - Ruskoaho, Heikki

AU - Rysä, Jaana

PY - 2015

Y1 - 2015

N2 - 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 α-actin to cardiac α-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 α-actin to cardiac α-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 α-actin to cardiac α-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 α-actin isoform ratio.

AB - 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 α-actin to cardiac α-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 α-actin to cardiac α-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 α-actin to cardiac α-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 α-actin isoform ratio.

U2 - 10.1371/journal.pone.0130502

DO - 10.1371/journal.pone.0130502

M3 - Article

C2 - 26098115

VL - 10

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 6

M1 - e0130502

ER -