Aortic valve leaflet glycosaminoglycans composition and modification in severe chronic valve regurgitation

Background and aim of the study: The surgical segments of aortic valve leaflets from patients with severe chronic aortic regurgitation were analyzed (by percentage and structure) for their content of complex polysaccharides and glycosaminoglycans (GAGs), and compared with control segments. Methods: The GAG, hyaluronic acid (HA), chondroitin sulfate (CS) and dermatan sulfate (DS) and disaccharide contents were determined in segments (leaflet, root attachment region and belly) of aortic valve leaflets (non-coronary, left coronary and right coronary) using a multi-analytical approach. Results: The aortic valve leaflets showed the presence of HA and CS/DS, with an overall charge density of ~0.51-0.55. The CS/DS polymers showed a 4-sulfated/6-sulfated ratio of ~0.70-0.77 in the belly, and ~1.60-1.72 in commissure parts (~+124%). The total amount of GAGs was ~1.60-2.40 μg/mg of tissue. A significant increase in sulfated GAGs was observed in all valve parts in patients suffering from severe aortic insufficiency, as well as an increase in the 4-sulfated/6-sulfated ratio in the leaflet belly (~+102%). Conclusion: It is speculated that differences in 4- sulfated/6-sulfated ratio determined in the belly and leaflet attachment region-commissure parts of the leaflets may correlate with the tensile or compressive loading of normal aortic valve regions. At the same time, it may be assumed that the increase in sulfated GAGs and 4-sulfated/6-sulfated ratio in the leaflet belly of valves taken from patients suffering severe aortic insufficiency was consistent with an altered matrix microstructure capable of influencing the hydration of these pathological tissues, and of conditioning their mechanical weakness.