Human abdominal aortic aneurysm is characterized by decreased versican concentration and specific downregulation of versican isoform V-0

Abdominal aortic aneurysm (AAA) is a common disease of human aorta with inc reased incidence. It is a complication to atherosclerosis acid it is closel y associated with alterations in extracellular macromolecules. In this: stu dy, the levels of mRNA For versican - the major extracellular arterial prot eoglycan (PC) - present in AAA and normal aortas were evaluated bq reverse- transcriptase polymerase chain reaction. The concentration of versican was also examined in corresponding tissue samples. Versican was almost complete ly extracted with 4 M guanidine hydrochloride in the presence of Triton X-1 00, isolated by chromatography on DEAE-Sephacel and characterized using tre atment with specific chondro-/dermato-lyases and agarose gel electrophoresi s. Versican localization in tissue as well as the variation and distributio n of smooth muscle cells (SMCs) and macrophages were also investigated immu nohistochemically. The mRNAs coding for versican isoforms V-0 and V-1 were identified in both tissues. whereas V-2 was absent. The expression of V-0 w as decreased 40% in aneurysmal vessel wall, whereas that for V-1 remained c onstant. This change was simultaneous with a significant decrease in versic an concentration by 89%. In normal aortas, most versican was seen in the in tima, whereas in AAA, this layer is characterized by advanced atherosclerot ic lesion, rich in lipids and macrophages: but poor in versican. The decrea sed transcription and the still lower amount of versican in the AAA may cor relate to (i) a decrease in density of SMCs, these cells bring the major so urce of versican in aorta, and (ii) the presence of macrophages, which may induce versican degradation and modulate versican synthesis. It is proposed that the decreased synthesis and increased degradation of versican, partic ularly of isoform V-0, and the resulting low concentration in the intima ar t: crucial Factors contributing to the altered viscoelastic and compressive properties and thereby to the deformity and dilatation of aorta. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.