The dermatan sulfate-dependent anticoagulant pathway is mostly preserved in aneurysm and in severe atherosclerotic lesions while the heparan sulfate pathway is disrupted

Abstract

BackgroundThe pathogenesis of abdominal aortic aneurysm is associated with changes of several components of arterial wall. Vascular glycosaminoglycans contribute to the non-thrombogenic activity of blood vessels. We investigated whether modifications of glycosaminoglycans in human abdominal aortic aneurysm affect their anticoagulant properties. MethodsGlycosaminoglycans were extracted from abdominal aortic aneurysms (n=11) derived from reconstitution surgeries, human abdominal aortas (n=9) from normal organ transplant donors and from preserved (n=10) and atherosclerotic (n=17) segments obtained from autopsy of an old patient. Glycosaminoglycan composition, concentration and anticoagulant activity were determined. ResultsGlycosaminoglycans extracted from aneurysms have a more potent anticoagulant activity than those from normal arteries of young adults, mostly due to a relative enrichment of dermatan sulfate, which potentiates heparin cofactor II inhibition of thrombin. Arterial segments of aged patient with severe atherosclerosis showed a glycosaminoglycan composition similar to aneurysms samples. Glycosaminoglycans extracted from these regions showed also a more potent heparin cofactor II-dependent anticoagulant activity than lesion-free areas due to the relative enrichment of dermatan sulfate. ConclusionThe anticoagulant activity from abdominal aortic aneurysms is preserved. No modifications particular to the aneurysms were dissociated from those observed in atherosclerosis.