Synergistic cardiac pathological hypertrophy induced by high-salt diet in IGF-IIRα cardiac-specific transgenic rats

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere0216285
JournalPLoS ONE
Volume14
Issue number6
DOIs
Publication statusPublished - Jun 1 2019

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Transgenic Rats
Cardiomegaly
Nutrition
hypertrophy
Rats
insulin
Salts
genetically modified organisms
Insulin
Diet
salts
receptors
rats
Growth
diet
Hypertrophy
Up-Regulation
Sirtuin 1
NFATC Transcription Factors
Angiotensin I

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Chang, R. L., Nithiyanantham, S., Huang, C. Y., Pai, P. Y., Chang, T. T., Hu, L. C., ... Huang, C. Y. (2019). Synergistic cardiac pathological hypertrophy induced by high-salt diet in IGF-IIRα cardiac-specific transgenic rats. PLoS ONE, 14(6), [e0216285]. https://doi.org/10.1371/journal.pone.0216285

Synergistic cardiac pathological hypertrophy induced by high-salt diet in IGF-IIRα cardiac-specific transgenic rats. / Chang, Ruey Lin; Nithiyanantham, Srinivasan; Huang, Chih Yang; Pai, Pei Ying; Chang, Tung Ti; Hu, Lai Chin; Chen, Ray Jade; VijayaPadma, V.; Kuo, Wei Wen; Huang, Chih Yang.

In: PLoS ONE, Vol. 14, No. 6, e0216285, 01.06.2019.

Research output: Contribution to journalArticle

Chang, RL, Nithiyanantham, S, Huang, CY, Pai, PY, Chang, TT, Hu, LC, Chen, RJ, VijayaPadma, V, Kuo, WW & Huang, CY 2019, 'Synergistic cardiac pathological hypertrophy induced by high-salt diet in IGF-IIRα cardiac-specific transgenic rats', PLoS ONE, vol. 14, no. 6, e0216285. https://doi.org/10.1371/journal.pone.0216285
Chang, Ruey Lin ; Nithiyanantham, Srinivasan ; Huang, Chih Yang ; Pai, Pei Ying ; Chang, Tung Ti ; Hu, Lai Chin ; Chen, Ray Jade ; VijayaPadma, V. ; Kuo, Wei Wen ; Huang, Chih Yang. / Synergistic cardiac pathological hypertrophy induced by high-salt diet in IGF-IIRα cardiac-specific transgenic rats. In: PLoS ONE. 2019 ; Vol. 14, No. 6.
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