Aldosterone induces C-reactive protein expression via MR-ROS-MAPK-NF-κB signal pathway in rat vascular smooth muscle cells

• Aldosterone is able to exert a proinflammatory effect on vascular smooth muscle cells by inducing CRP expression.
• Molecular mechanism of aldosterone-induced CRP expression involves MR-ROS-ERK1/2-NF-κB signal pathway.
• The results provide a new explanation for proinflammatory and proatherosclerotic effects of aldosterone.

Atherosclerosis is a chronic inflammatory disease in the vessel. As a representative inflammatory cytokine, C-reactive protein (CRP) participates in atherogenesis. Although hyperaldosteronism is known to evoke inflammatory response in several tissues and cell types, there is no direct evidence to demonstrate the proinflammatory effect of aldosterone on vascular smooth muscle cells (VSMCs) through CRP. In this study, we observed the effect of aldosterone on CRP expression and the molecular mechanisms in rat VSMCs. The results showed that aldosterone induced CRP expression in VSMCs in vitro and in vivo. Mineralocorticoid receptor (MR) antagonist spironolactone abolished aldosterone-induced CRP expression. In addition, aldosterone stimulated generation of reactive oxygen species (ROS) and activated ERK1/2 phosphorylation, whereas spironolactone inhibited aldosterone-stimulated ROS generation and ERK1/2 phosphorylation. Antioxidant NAC decreased aldosterone-induced CRP expression and ERK1/2 phosphorylation. The further study confirmed that ERK1/2 inhibitor PD98059 and NF-κB inhibitor pyrrolidine dithiocarbamate both depressed aldosterone-induced CRP expression. These demonstrate that aldosterone is able to induce CRP expression via MR-ROS-ERK1/2-NF-κB signal pathway in VSMCs, which provides a new evidence for the proinflammatory and proatherosclerotic effects of aldosterone.