Key result
IGF-IIRα overexpression in a transgenic rat model aggravated high-salt induced cardiac apoptosis and fibrosis, leading to a decline in ejection fraction and fractional shortening.
Why the study?
IGF-IIR activation regulates cardiac remodeling leading to apoptosis, prompting investigation into the role of a novel truncated transcript, IGF-IIRalpha, under high-salt conditions.
Does IGF-IIRα overexpression aggravate cardiac apoptosis and fibrosis under high-salt conditions in transgenic rats?
Does IGF-IIRα overexpression aggravate cardiac apoptosis and fibrosis under high-salt conditions in transgenic rats?
IGF-IIRα overexpression promotes cardiac apoptosis and fibrosis, particularly under high-salt conditions, highlighting a potential mechanism for salt-induced cardiotoxicity.
IGF-IIR activation regulates cardiac remodeling leading to apoptosis. Here, we identified the novel IGF-IIRα (150 KDa), a truncated IGF-IIR transcript enhances cardiac apoptosis under high-salt uptake in transgenic rat model. Echocardiographic analysis revealed decline in ejection fraction and fractional shortening percentage in IGF-IIRα (TG) rats. We found that IGF-IIRα TG rats developed severe apoptosis and fibrosis as identified through TUNEL assay and Masson's trichrome staining. Importantly, the heart functioning, apoptosis, and fibrosis were significantly affected under high-salt conditions in IGF-IIRα (TG) rats. Significant upregulation of apoptosis was evident from decreased Bcl-2, p-AKT, and p-PI3K expressions with concomitant increase in Bad, cytochrome C, cleaved caspase 3 levels. We found that, IGF-IIRα highly induced tissue fibrosis through collagen accumulation (col I, col III) and up regulated various fibrotic markers such as tPA, uPA, TGF-β, and vimentin expressions. The observed upregulation of fibrosis were significantly regulated under high-salt conditions and their over regulation under IGF-IIRα over expressions shows the key role of IGF-IIRα in promoting high-salt induced fibrosis. During IGF-IIRα over expression induced cardiotoxicity, under high salt condition, and it destroys the interaction between CHIP and HSF1, which promotes the degradation of HSF1 and results in upregulation of IGF-IIR/IGF-IIRα expressions. Altogether, the study unveils novel IGF-IIRα in the regulation of cardiac apoptosis and fibrosis under high-salt diet.
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Chang et al. (2018) studied Cardiac remodeling, apoptosis, and fibrosis. IGF-IIRα overexpression and high-salt diet was evaluated on Cardiac apoptosis and fibrosis. IGF-IIRα overexpression in a transgenic rat model aggravated high-salt induced cardiac apoptosis and fibrosis, leading to a decline in ejection fraction and fractional shortening.
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