Myocardial toxicity induced by silica nanoparticles in a transcriptome profile

The deleterious effects of silica nanoparticles (SiNPs) on human health and the ecological system have gradually gained attention owing to their heavy annual output and extensive global flux. The updated epidemiological or experimental investigations have demonstrated the potential myocardial toxicity triggered by SiNPs, but the underlying mechanisms and long-lasting cardiac effects are still poorly understood. Here, a rat model of sub-chronic respiratory exposure to SiNPs was conducted, and the histopathological analysis and ultrastructural investigation of heart tissues were carried out. More importantly, a comprehensive analysis of whole-genome transcription was utilized in rat heart to uncover key biological and cellular mechanisms triggered by SiNPs. The widening of myocardial space and partial fiber rupture were clearly manifested in rat heart after prolonged SiNPs exposure, particularly accompanied by mitochondrial swelling and cristae rupture. With the aid of Affymetrix GeneChips, 3153 differentially expressed genes (DEGs) were identified after SiNPs exposure, including 1916 down- and 1237 up-regulated genes. GO and KEGG analysis illustrated many important biological processes and pathways perturbed by SiNPs, mainly specializing in cellular stress, energy metabolism, actin filament dynamics and immune response. Signal-net analysis revealed that Prkaca (PKA) plays a core role in the cardiac toxification process of prolonged exposure of SiNPs to rats. Furthermore, qRT-PCR verified that PKA-mediated calcium signaling is probably responsible for SiNPs-induced cardiac injury. Conclusively, our study revealed that SiNPs caused myocardial injury, and particularly, provided transcriptomic insight into the role of PKA-calcium signaling triggered by SiNPs, which would facilitate SiNPs-based nanosafety assessment and biomedicine development.