Abstract
Reactive oxygen species‑induced cyclophilin A (CyPA) release from vascular smooth muscle cells (VSMCs) may be inhibited by simvastatin in vitro. The present study aimed to further examine the effect of simvastatin on serum CyPA levels and the basigin (CD147)‑extracellular signal‑regulated kinase (ERK) 1/2‑cyclin pathway during thoracic aorta remodeling. The mechanisms through which simvastatin may inhibit CyPA secretion from VSMCs were further investigated. Serum CyPA levels and the expression kinetics of CyPA‑associated signaling pathways were examined following simvastatin treatment in rat thoracic aortas during hypertension. Cell lysates were prepared from middle layer of thoracic aortas at 1, 4, 8 and 12 weeks subsequent to surgery. ELISA analysis revealed that serum CyPA levels were gradually increased with the progression of thoracic aorta remodeling. Western blotting demonstrated that the expression of CD147, phosphorylated‑ERK1/2, cyclin D1, cyclin A, and cyclin E were increased with the progression of thoracic aorta remodeling. Simvastatin administration for 4, 8 and 12 weeks diminished all these changes, as observed in the hypertensive group. VSMCs from simvastatin‑treated rats secreted a decreased amount of CyPA compared with VSMCs from hypertensive rats. In addition, pretreatment with geranylgeraniol partly reversed the inhibitory effect of simvastatin on LY83583‑induced CyPA secretion in cultured VSMCs, whereas GGTI‑298 and KD025 [a selective Rho‑associated protein kinase 2 (ROCK2) inhibitor] mimicked the inhibitory effect of simvastatin. The present study demonstrated that simvastatin alleviated thoracic aorta remodeling by reducing CyPA secretion and expression of the CD147‑ERK1/2‑cyclin signaling pathway. In addition, the results of the present study demonstrated that the Rho‑ROCK2 pathway mediated CyPA secretion from VSMCs.