Decreased expression of P54nrb/NonO correlates with collagen deposition and fibrosis in human aortic dissection

Abstract

Aortic dissection (AD) is characterized by changes in the extracellular matrix, including fibrosis with collagen production. P54(nrb) /NonO is known to be involved in collagen formation. In this study, we examined whether AD is associated with abnormal P54(nrb) /NonO expression. Aortic specimens and serum were obtained from 10 patients with AD and 10 controls. In-vitro cultures of vascular smooth muscle cells (VSMCs) and adventitial fibroblasts (AFs) were obtained from organ donors. P54(nrb) /NonO protein and mRNA levels were determined by Western blot, immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (quantitative real-time RT-PCR). To evaluate collagen expression, we stained tissue sections with Masson's trichrome. Serum concentration of TNF-α was determined by enzyme-linked immunosorbent assay (ELISA). Aortic P54(nrb) /NonO protein and mRNA were decreased in AD patients, compared with controls. Decreased P54(nrb) /NonO mRNA correlated significantly with increased collagen deposition and fibrosis in AD aortas. In VSMCs and AFs from normal human aortas, P54(nrb) /NonO was expressed strongly and localized to the nucleus. Patients with AD exhibited significantly decreased expression of P54(nrb) /NonO. The significant correlation between P54(nrb) /NonO and collagen may point to novel thinking about collagen metabolism research in AD aorta.