synergistic cardiac pathological hypertrophy induced by high-salt diet in igf-iirα cardiac-specific transgenic rats.
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ID: 147193
2019
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Abstract
Stress-induced cardiac hypertrophy leads to heart failure. Our previous studies demonstrate that insulin-like growth factor-II receptor (IGF-IIR) signaling is pivotal to hypertrophy regulation. In this study, we show a novel IGF-IIR alternative spliced transcript, IGF-IIRα (150 kDa) play a key role in high-salt induced hypertrophy mechanisms. Cardiac overexpression of IGF-IIRα and high-salt diet influenced cardiac dysfunction by increasing pathophysiological changes with up-regulation of hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). We found that, cardiac hypertrophy under high-salt conditions were amplified in the presence of IGF-IIRα overexpression. Importantly, high-salt induced angiotensin II type I receptor (AT1R) up regulation mediated IGF-IIR expressions via upstream mitogen activated protein kinase (MAPK)/silent mating type information regulation 2 homolog 1 (SIRT1)/heat shock factor 1 (HSF1) pathway. Further, G-coupled receptors (Gαq) activated calcineurin/nuclear factor of activated T-cells, cytoplasmic 3 (NFATc3)/protein kinase C (PKC) signaling was significantly up regulated under high-salt conditions. All these effects were observed to be dramatically over-regulated in IGF-IIRα transgenic rats fed with a high-salt diet. Altogether, from the findings, we demonstrate that IGF-IIRα plays a crucial role during high-salt conditions leading to synergistic cardiac hypertrophy.
| Reference Key |
chang2019plossynergistic
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|---|---|
| Authors | ;Ruey-Lin Chang;Srinivasan Nithiyanantham;Chih-Yang Huang;Pei-Ying Pai;Tung-Ti Chang;Lai-Chin Hu;Ray-Jade Chen;V VijayaPadma;Wei-Wen Kuo;Chih-Yang Huang |
| Journal | ensaio pesquisa em educação em ciências |
| Year | 2019 |
| DOI |
10.1371/journal.pone.0216285
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| URL | |
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