Description:
The deleterious effects of silica nanoparticles (SiNPs) on human health and ecological system have gradually gained concerns owing to its heavily 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 is 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 with 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 Prkaca (PKA) acting a core role in the cardiac toxification process of SiNPs prolonged exposure to rats. Further, qRT-PCR verified PKA-mediated calcium signaling probably responsible for SiNPs-induced cardiac injury. Conclusively, our study revealed SiNPs caused myocardial injury, and particularly, provided transcriptomic insight on the role of PKA-calcium signaling triggered by SiNPs, which would facilitate SiNPs-based nanosafety assessment and biomedicine development