High-salt/hyperosmotic stress induces cardiomyocyte hypertrophy via the PI3K/AKT signaling pathway
Year: 2026
Type: article
Abstract: High-salt exposure is linked to maladaptive cardiac remodeling, but its underlying transcriptional mechanisms remain unclear. We investigated the effects of NaCl-supplemented high-salt/hyperosmotic stress (final Na + concentration: 190-210 mM) on H9c2 cells. NaCl supplementation induced a distinct hypertrophic phenotype, most pronounced at 210 mM for 48 h, characterized by increased cell surface area, elevated protein levels of ANP and α-SMA, and upregulated mRNA expression of classic hypertrophic markers (ANP, BNP, and Myh7). Bulk RNA-seq identified 2125 differentially expressed genes under 210 mM NaCl conditions. Functional enrichment and protein-protein interaction analyses revealed that upregulated genes were significantly enriched in extracellular matrix (ECM)-receptor interaction and PI3K/AKT signaling, suggesting potential integrin-mediated links. Experimentally, high-salt/hyperosmotic stress increased AKT phosphorylation (p-AKT), whereas pharmacological PI3K inhibition via LY294002 (5 μM) reduced p-AKT, downregulated ANP, and attenuated cell enlargement. In conclusion, high-salt/hyperosmotic conditions drive H9c2 cell hypertrophy and transcriptomic remodeling, implicating ECM-integrin signaling and PI3K/AKT activation. These in vitro findings provide preliminary mechanistic insights into salt-induced cardiac injury, though further validation using osmotic controls and in vivo models is required.
Source: Scientific Reports
Authors: Mingming Huang, Zhenlin Liu, Yutao Wei, Xiaobo Wang, Lihua Li
Institution: Dali University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W7165061010