Decreased Tissue Levels of Cyclophilin A, a Cyclosporine A Target and Phospho-ERK1/2 in Simvastatin Patients with Abdominal Aortic Aneurysm

Abstract

Background: Cyclophilin A (CyPA), a cyclosporine A-binding protein, influences abdominal aortic aneurysm (AAA) formation and the ERK1/2 signalling pathway in animal and in vitro studies. Statins decrease CyPA in smooth muscle cells although their influence on CyPA in human AAA is unknown. Material and methods: The study was performed on AAA wall-tissue samples obtained from 30 simvastatintreated and 15 non-statin patients (2:1 case to control). The patients were matched by age, sex and AAA diameter. We investigated the gene expression of CyPA, its receptor extracellular matrix metalloproteinase inducer (EMMPRIN) by real-time RT-PCR. CyPA and EMMPRIN protein level and phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) were measured by Western blot. Results: The AAA wall tissue from simvastatin-treated patients had significantly lower CyPA gene expression and protein levels (P ¼ 0.0018, P ¼ 0.0083, respectively). Furthermore, phosphorylation of ERK1 and ERK2 was markedly suppressed in the simvastatin group (P ¼ 0.0002, P ¼ 0.0027, respectively). However, simvastatin did not influence EMMPRIN gene and protein expression. Conclusion: Simvastatin-treated patients with AAA exert lower CyPA messenger RNA (mRNA), as well as CyPA intracellular protein levels and a decreased amount of phospho-ERK1/2. Thus, the interference with signalling pathways leading to CyPA formation and ERK1/2 activation reveals a new anti-inflammatory role of statins in AAA.