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

Sárközy, Márta and Gáspár, Renáta and Zvara, Ágnes and Siska, Andrea and Kővári, Bence and Szűcs, Gergő and Márványkövi, Fanni and Kovács, Mónika Gabriella and Diószegi, Petra and Bodai, László and Zsindely, Nóra and Pipicz, Márton and Gömöri, Kamilla and Kiss, Krisztina and Bencsik, Péter and Cserni, Gábor and Puskás, G. László and Földesi, Imre and Bátkai, Sándor and Csont, Tamás Bálint (2019) Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212. Scientific reports, 9. No.-1302. ISSN 2045-2322


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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.

Item Type: Article
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
Depositing User: MTMT SWORD
Date Deposited: 24 Sep 2019 08:03
Last Modified: 24 Sep 2019 08:03

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