Cystic medial degeneration of the aorta is associated with p53 accumulation, Bax upregulation, apoptotic cell death, and cell proliferation

Objective-To address a potential role for p53, Bc12 associated protein X (B ax), and apoptosis in the processes associated with cell turnover during cy stic medial degeneration (CMD) of the aorta, Methods-Histochemical, immunohistochemical, biochemical, and morphometric m ethods were used to assess the presence and distribution of p53 immunoreact ivity (p53-IR) and Bar immunoreactivity (Bax-IR), as well as the presence o f apoptosis and tissue repair processes. Results-Immunohistochemical staining disclosed evidence for p53-IR in all s pecimens in 26.1 (11.5)% of vascular smooth muscle cells (VSMCs) (controls 0.8 (1.3)%; p < 0.001). Bax-IR was present in all specimens in 10 (5.4)% of medial cells (controls 0.3 (0.5)%; p < 0.001). Medial VSMCs (a-actin posit ive) with cytoplasmic staining for an apoptosis specific protein (c-jun/ASP ) were present in 20/20 specimens (0.7 (0.6)% of VSMCs, controls 0%, p < 0. 001), whereas terminal deoxynucleotidyl transferase mediated dUTP-biotin ni ck end labeling (TUNEL) positive VSMCs were present in 17/20 specimens (1 ( 1.5)% of VSMCs,controls 0%, p < 0.001). The presence of apoptosis was confi rmed by electron microscopy and the demonstration of oligonucleosomal DNA f ragments after agarose gel electrophoresis. As shown by double labeling and investigation of serial sections, p53-IR, Bax-IR, c-jun/ASP-IR, and positi ve TUNEL labeling localised to the same compartments of the aortic media, r aising a possible role for p53 and Bar in the triggering of apoptosis of VS MC during CMD. MIB1/Ki-67 positive medial VSMCs (a-actin positive) and mese nchymal cells (vimentin positive) were present in all specimens (2.5 (2.8)% of medial cells; controls 0.3 (0.9)%, p < 0.001) mainly in the region arou nd the vasa vasorum, indicating that cell. regeneration during CMD may orig inate mainly from the mesenchyme surrounding the vasa vasorum. Conclusion-This study shows that the formal pathogenesis of CMD is characte rised by p53 accumulation, Bar upregulation, cell death by apoptosis, and c ell regeneration, Nevertheless, the precise stimuli of p53 activation and B ar upregulation as well as the role of p53 and apoptosis in the dissection process itself remain elusive.