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Distinct defects in collagen microarchitecture underlie vessel-wall failure in advanced abdominal aneurysms and aneurysms in Marfan syndrome

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Author: Lindeman, J.H.N. · Ashcroft, B.A. · Beenakker, J.-W.M. · Es, M. van · Koekkoek, N.B.R. · Prins, F.A. · Tielemans, J.F. · Abdul-Hussien, H. · Bank, R.A. · Oosterkamp, T.H.
Institution: TNO Kwaliteit van Leven
Source:Proceedings of the National Academy of Sciences of the United States of America, 2, 107, 862-865
Identifier: 347467
Keywords: Biology · Biomedical Research · collagen · abdominal aorta aneurysm · adult · aged · article · atomic force microscopy · clinical article · collagen defect · controlled study · human · human tissue · Marfan syndrome · priority journal · protein analysis · protein structure · Aged · Aorta, Abdominal · Aortic Aneurysm, Abdominal · Arteries · Collagen · Humans · Hydroxyproline · Marfan Syndrome · Microscopy, Confocal · Middle Aged · Proline


An aneurysm of the aorta is a common pathology characterized by segmentalweakeningof the artery.Althoughit isgenerally accepted that the vessel-wall weakening is caused by an impaired collagen metabolism, a clear association has been demonstrated only for rare syndromes such as the vascular type Ehlers-Danlos syndrome. Here we show that vessel-wall failure in growing aneurysms of patients who have aortic abdominal aneurysm (AAA) or Marfan syndrome is not related to a collagen defect at the molecular level. On the contrary our findings indicate similar (Marfan) or even higher collagen concentrations (AAA) and increased collagen cross-linking in the aneurysms. Using 3D confocal imaging we show that the two conditions are associated with profound defects in collagen microarchitecture. Reconstructions of normal vesselwall showthat adventitial collagen fibers are organized in a loose braiding of collagen ribbons. These ribbons encage the vessel, allowing the vessel to dilate easily but preventing overstretching. AAA and aneurysms in Marfan syndrome show dramatically altered collagen architectures with loss of the collagen knitting. Evaluations of the functional characteristics by atomic force microscopy showed that the wall has lost its ability to stretch easily and revealed a second defect: although vascular collagen in normal aorticwall behaves as a coherent network, inAAAand Marfan tissues it does not. As result, mechanical forces loaded on individual fibers are not distributed over the tissue. These studies demonstrate that the mechanical properties of tissue are strongly influenced by collagen microarchitecture and that perturbations in the collagen networks may lead to mechanical failure.