Key result
IGF-IIRα overexpression plus high salt synergistically increases cardiac hypertrophy ~45% in rats.
Why the study?
The role of the novel IGF-IIR alternative spliced transcript IGF-IIRα in high-salt diet induced cardiac hypertrophy mechanisms was not previously understood.
IGF-IIRα plays a crucial role in mediating synergistic cardiac pathological hypertrophy under high-salt conditions in a transgenic rat model.
Findings from this rodent model should not change clinical practice; leaves open IGF-IIRα as a potential target in salt-induced hypertrophy.
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.
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Chang et al. (2019) studied Cardiac hypertrophy (n=24). IGF-IIRα overexpression and high-salt diet vs. Wild-type rats on normal diet was evaluated on Whole heart weight to body weight ratio (WHW/BW × 10³) (p=<0.001). Cardiac overexpression of IGF-IIRα combined with a high-salt diet synergistically induced pathological cardiac hypertrophy, significantly increasing the whole heart weight to body weight ratio compared to wild-type rats.
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