z-logo
Premium
The combined inhibition of the CaMKIIδ and calcineurin signaling cascade attenuates IGF‐IIR‐induced cardiac hypertrophy
Author(s) -
Chen ChungHao,
Lin JingWei,
Huang ChihYang,
Yeh YuLan,
Shen ChiaYao,
Badrealam Khan Farheen,
Ho TsungJung,
Padma V. Vijaya,
Kuo WeiWen,
Huang ChihYang
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29242
Subject(s) - calcineurin , muscle hypertrophy , signal transduction , endocrinology , medicine , biology , microbiology and biotechnology , transplantation
Cardiac hypertrophy is a common phenomenon observed in progressive heart disease associated with heart failure. Insulin‐like growth factor receptor II (IGF‐IIR) has been much implicated in myocardial hypertrophy. Our previous studies have found that increased activities of signaling mediators, such as calcium/calmodulin‐dependent protein kinase II (CaMKII) and calcineurin induces pathological hypertrophy. Given the critical roles played by CaMKII and calcineurin signaling in the progression of maladaptive hypertrophy, we anticipated that inhibition of CaMKII and calcineurin signaling may attenuate IGF‐IIR‐induced cardiac hypertrophy. The current study, therefore, investigated the effects of IGF‐IIR activation on the CaMKII and calcineurin signaling and whether the combinatorial inhibition of the CaMKIIδ and calcineurin signaling could ameliorate IGF‐IIR‐induced pathological hypertrophy. In the present study, we induced IGF‐IIR through the cardiomyocyte‐specific transduction of IGFII Y27L via adeno‐associated virus 2 (AAV2) to evaluate its effects on cardiac hypertrophy. Interestingly, it was observed that the activation of IGF‐IIR signaling through IGFII Y27L induces significant hypertrophy of the myocardium and increased cardiac apoptosis and fibrosis. Moreover, we found that Leu 27 IGF‐II significantly induced calcineurin and CaMKII expression. Furthermore and importantly, the combinatorial treatment with CaMKII and calcineurin inhibitors significantly alleviates IGF‐IIR‐induced hypertrophic responses. Thus, it could be envisaged that the inhibition of IGF‐IIR may serve as a promising candidate for attenuating maladaptive hypertrophy. Both calcineurin and CaMKII could be valuable targets for developing treatment strategies against hypertension‐induced cardiomyopathies.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here