Heart 1999;82:286-293 ( September )

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

C Ihling^a, T Szombathy^b, K Nampoothiri^c, J Haendeler^d, F Beyersdorf^e, M Uhl^f, A M Zeiher^d, H E Schaefer^a

^a Department of Pathology, University of Freiburg, Albertstrae 19, D-79104 Freiburg, Germany, ^b 3rd Department of Internal Medicine, Semmelweis University of Budapest, Budapest, Hungary, ^c Department of Zoology, Sanathana Dharma College, Alappuzha, Kerala, India, ^d Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany, ^e Department of Cardiovascular Surgery, University of Freiburg, Freiburg, Germany, ^f Department of Radiology, University of Freiburg

Correspondence to: Dr Ihling. email: chihlpa{at}asl.com

Accepted for publication 19 March 1999

OBJECTIVETo address a potential role for p53, Bcl2 associated protein X (Bax), and apoptosis in the processes associated with cell turnover during cystic medial degeneration (CMD) of the aorta.
METHODSHistochemical, immunohistochemical, biochemical, and morphometric methods were used to assess the presence and distribution of p53 immunoreactivity (p53-IR) and Bax immunoreactivity (Bax-IR), as well as the presence of apoptosis and tissue repair processes.
RESULTSImmunohistochemical staining disclosed evidence for p53-IR in all specimens 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 (-actin positive) 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 nick 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 confirmed by electron microscopy and the demonstration of oligonucleosomal DNA fragments after agarose gel electrophoresis. As shown by double labeling and investigation of serial sections, p53-IR, Bax-IR, c-jun/ASP-IR, and positive TUNEL labeling localised to the same compartments of the aortic media, raising a possible role for p53 and Bax in the triggering of apoptosis of VSMC during CMD. MIB1/Ki-67 positive medial VSMCs (-actin positive) and mesenchymal 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 around the vasa vasorum, indicating that cell regeneration during CMD may originate mainly from the mesenchyme surrounding the vasa vasorum.
CONCLUSIONThis study shows that the formal pathogenesis of CMD is characterised by p53 accumulation, Bax upregulation, cell death by apoptosis, and cell regeneration. Nevertheless, the precise stimuli of p53 activation and Bax upregulation as well as the role of p53 and apoptosis in the dissection process itself remain elusive.


Keywords: mucoid cystic medial degeneration of the aorta; p53 accumulation; apoptosis; cell proliferation

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© 1999 by Heart
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