Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212

Márta Sárközy, Renáta Gáspár, A. Zvara, Andrea Siska, Bence Kővári, Gergő Szűcs, Fanni Márványkövi, Mónika G. Kovács, Petra Diószegi, L. Bodai, Nóra Zsindely, Márton Pipicz, Kamilla Gömöri, Krisztina Kiss, Péter Bencsik, G. Cserni, L. Puskás, I. Földesi, Thomas Thum, Sándor BátkaiT. Csont

Research output: Article

1 Citation (Scopus)

Abstract

Chronic kidney disease (CKD) is a public health problem that increases the risk of cardiovascular morbidity and mortality. Heart failure with preserved ejection fraction (HFpEF) characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction is a common cardiovascular complication of CKD. MicroRNA-212 (miR-212) has been demonstrated previously to be a crucial regulator of pathologic LVH in pressure-overload-induced heart failure via regulating the forkhead box O3 (FOXO3)/calcineurin/nuclear factor of activated T-cells (NFAT) pathway. Here we aimed to investigate whether miR-212 and its hypertrophy-associated targets including FOXO3, extracellular signal-regulated kinase 2 (ERK2), and AMP-activated protein kinase (AMPK) play a role in the development of HFpEF in CKD. CKD was induced by 5/6 nephrectomy in male Wistar rats. Echocardiography and histology revealed LVH, fibrosis, preserved systolic function, and diastolic dysfunction in the CKD group as compared to sham-operated animals eight and/or nine weeks later. Left ventricular miR-212 was significantly overexpressed in CKD. However, expressions of FOXO3, AMPK, and ERK2 failed to change significantly at the mRNA or protein level. The protein kinase B (AKT)/FOXO3 and AKT/mammalian target of rapamycin (mTOR) pathways are also proposed regulators of LVH induced by pressure-overload. Interestingly, phospho-AKT/total-AKT ratio was increased in CKD without significantly affecting phosphorylation of FOXO3 or mTOR. In summary, cardiac overexpression of miR-212 in CKD failed to affect its previously implicated hypertrophy-associated downstream targets. Thus, the molecular mechanism of the development of LVH in CKD seems to be independent of the FOXO3, ERK1/2, AMPK, and AKT/mTOR-mediated pathways indicating unique features in this form of LVH.

Original languageEnglish
Article number1302
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - dec. 1 2019

Fingerprint

MicroRNAs
Chronic Renal Insufficiency
Left Ventricular Hypertrophy
Sirolimus
AMP-Activated Protein Kinases
Heart Failure
Mitogen-Activated Protein Kinase 1
Hypertrophy
NFATC Transcription Factors
Pressure
Proto-Oncogene Proteins c-akt
Calcineurin
Nephrectomy
Echocardiography
Wistar Rats
Histology
Fibrosis
Public Health
Phosphorylation
Morbidity

ASJC Scopus subject areas

  • General

Cite this

Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212. / Sárközy, Márta; Gáspár, Renáta; Zvara, A.; Siska, Andrea; Kővári, Bence; Szűcs, Gergő; Márványkövi, Fanni; Kovács, Mónika G.; Diószegi, Petra; Bodai, L.; Zsindely, Nóra; Pipicz, Márton; Gömöri, Kamilla; Kiss, Krisztina; Bencsik, Péter; Cserni, G.; Puskás, L.; Földesi, I.; Thum, Thomas; Bátkai, Sándor; Csont, T.

In: Scientific reports, Vol. 9, No. 1, 1302, 01.12.2019.

Research output: Article

Sárközy, M, Gáspár, R, Zvara, A, Siska, A, Kővári, B, Szűcs, G, Márványkövi, F, Kovács, MG, Diószegi, P, Bodai, L, Zsindely, N, Pipicz, M, Gömöri, K, Kiss, K, Bencsik, P, Cserni, G, Puskás, L, Földesi, I, Thum, T, Bátkai, S & Csont, T 2019, 'Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212', Scientific reports, vol. 9, no. 1, 1302. https://doi.org/10.1038/s41598-018-37690-5
Sárközy, Márta ; Gáspár, Renáta ; Zvara, A. ; Siska, Andrea ; Kővári, Bence ; Szűcs, Gergő ; Márványkövi, Fanni ; Kovács, Mónika G. ; Diószegi, Petra ; Bodai, L. ; Zsindely, Nóra ; Pipicz, Márton ; Gömöri, Kamilla ; Kiss, Krisztina ; Bencsik, Péter ; Cserni, G. ; Puskás, L. ; Földesi, I. ; Thum, Thomas ; Bátkai, Sándor ; Csont, T. / Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212. In: Scientific reports. 2019 ; Vol. 9, No. 1.
@article{bdd18a90c66b439bbf03692b343c341c,
title = "Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212",
abstract = "Chronic kidney disease (CKD) is a public health problem that increases the risk of cardiovascular morbidity and mortality. Heart failure with preserved ejection fraction (HFpEF) characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction is a common cardiovascular complication of CKD. MicroRNA-212 (miR-212) has been demonstrated previously to be a crucial regulator of pathologic LVH in pressure-overload-induced heart failure via regulating the forkhead box O3 (FOXO3)/calcineurin/nuclear factor of activated T-cells (NFAT) pathway. Here we aimed to investigate whether miR-212 and its hypertrophy-associated targets including FOXO3, extracellular signal-regulated kinase 2 (ERK2), and AMP-activated protein kinase (AMPK) play a role in the development of HFpEF in CKD. CKD was induced by 5/6 nephrectomy in male Wistar rats. Echocardiography and histology revealed LVH, fibrosis, preserved systolic function, and diastolic dysfunction in the CKD group as compared to sham-operated animals eight and/or nine weeks later. Left ventricular miR-212 was significantly overexpressed in CKD. However, expressions of FOXO3, AMPK, and ERK2 failed to change significantly at the mRNA or protein level. The protein kinase B (AKT)/FOXO3 and AKT/mammalian target of rapamycin (mTOR) pathways are also proposed regulators of LVH induced by pressure-overload. Interestingly, phospho-AKT/total-AKT ratio was increased in CKD without significantly affecting phosphorylation of FOXO3 or mTOR. In summary, cardiac overexpression of miR-212 in CKD failed to affect its previously implicated hypertrophy-associated downstream targets. Thus, the molecular mechanism of the development of LVH in CKD seems to be independent of the FOXO3, ERK1/2, AMPK, and AKT/mTOR-mediated pathways indicating unique features in this form of LVH.",
author = "M{\'a}rta S{\'a}rk{\"o}zy and Ren{\'a}ta G{\'a}sp{\'a}r and A. Zvara and Andrea Siska and Bence Kőv{\'a}ri and Gergő Szűcs and Fanni M{\'a}rv{\'a}nyk{\"o}vi and Kov{\'a}cs, {M{\'o}nika G.} and Petra Di{\'o}szegi and L. Bodai and N{\'o}ra Zsindely and M{\'a}rton Pipicz and Kamilla G{\"o}m{\"o}ri and Krisztina Kiss and P{\'e}ter Bencsik and G. Cserni and L. Pusk{\'a}s and I. F{\"o}ldesi and Thomas Thum and S{\'a}ndor B{\'a}tkai and T. Csont",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-018-37690-5",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212

AU - Sárközy, Márta

AU - Gáspár, Renáta

AU - Zvara, A.

AU - Siska, Andrea

AU - Kővári, Bence

AU - Szűcs, Gergő

AU - Márványkövi, Fanni

AU - Kovács, Mónika G.

AU - Diószegi, Petra

AU - Bodai, L.

AU - Zsindely, Nóra

AU - Pipicz, Márton

AU - Gömöri, Kamilla

AU - Kiss, Krisztina

AU - Bencsik, Péter

AU - Cserni, G.

AU - Puskás, L.

AU - Földesi, I.

AU - Thum, Thomas

AU - Bátkai, Sándor

AU - Csont, T.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Chronic kidney disease (CKD) is a public health problem that increases the risk of cardiovascular morbidity and mortality. Heart failure with preserved ejection fraction (HFpEF) characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction is a common cardiovascular complication of CKD. MicroRNA-212 (miR-212) has been demonstrated previously to be a crucial regulator of pathologic LVH in pressure-overload-induced heart failure via regulating the forkhead box O3 (FOXO3)/calcineurin/nuclear factor of activated T-cells (NFAT) pathway. Here we aimed to investigate whether miR-212 and its hypertrophy-associated targets including FOXO3, extracellular signal-regulated kinase 2 (ERK2), and AMP-activated protein kinase (AMPK) play a role in the development of HFpEF in CKD. CKD was induced by 5/6 nephrectomy in male Wistar rats. Echocardiography and histology revealed LVH, fibrosis, preserved systolic function, and diastolic dysfunction in the CKD group as compared to sham-operated animals eight and/or nine weeks later. Left ventricular miR-212 was significantly overexpressed in CKD. However, expressions of FOXO3, AMPK, and ERK2 failed to change significantly at the mRNA or protein level. The protein kinase B (AKT)/FOXO3 and AKT/mammalian target of rapamycin (mTOR) pathways are also proposed regulators of LVH induced by pressure-overload. Interestingly, phospho-AKT/total-AKT ratio was increased in CKD without significantly affecting phosphorylation of FOXO3 or mTOR. In summary, cardiac overexpression of miR-212 in CKD failed to affect its previously implicated hypertrophy-associated downstream targets. Thus, the molecular mechanism of the development of LVH in CKD seems to be independent of the FOXO3, ERK1/2, AMPK, and AKT/mTOR-mediated pathways indicating unique features in this form of LVH.

AB - Chronic kidney disease (CKD) is a public health problem that increases the risk of cardiovascular morbidity and mortality. Heart failure with preserved ejection fraction (HFpEF) characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction is a common cardiovascular complication of CKD. MicroRNA-212 (miR-212) has been demonstrated previously to be a crucial regulator of pathologic LVH in pressure-overload-induced heart failure via regulating the forkhead box O3 (FOXO3)/calcineurin/nuclear factor of activated T-cells (NFAT) pathway. Here we aimed to investigate whether miR-212 and its hypertrophy-associated targets including FOXO3, extracellular signal-regulated kinase 2 (ERK2), and AMP-activated protein kinase (AMPK) play a role in the development of HFpEF in CKD. CKD was induced by 5/6 nephrectomy in male Wistar rats. Echocardiography and histology revealed LVH, fibrosis, preserved systolic function, and diastolic dysfunction in the CKD group as compared to sham-operated animals eight and/or nine weeks later. Left ventricular miR-212 was significantly overexpressed in CKD. However, expressions of FOXO3, AMPK, and ERK2 failed to change significantly at the mRNA or protein level. The protein kinase B (AKT)/FOXO3 and AKT/mammalian target of rapamycin (mTOR) pathways are also proposed regulators of LVH induced by pressure-overload. Interestingly, phospho-AKT/total-AKT ratio was increased in CKD without significantly affecting phosphorylation of FOXO3 or mTOR. In summary, cardiac overexpression of miR-212 in CKD failed to affect its previously implicated hypertrophy-associated downstream targets. Thus, the molecular mechanism of the development of LVH in CKD seems to be independent of the FOXO3, ERK1/2, AMPK, and AKT/mTOR-mediated pathways indicating unique features in this form of LVH.

UR - http://www.scopus.com/inward/record.url?scp=85061045858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061045858&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-37690-5

DO - 10.1038/s41598-018-37690-5

M3 - Article

C2 - 30718600

AN - SCOPUS:85061045858

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 1302

ER -