Differential proteoglycan and hyaluronan distribution in calcified aortic valves

Background: While the prevalence of calcified aortic valve disease continues to rise and no pharmacological treatments exist, little is known regarding the pathogenesis of the disease. Proteoglycans and the glycosaminoglycan hyaluronan are involved in calcification in arteriosclerosis and their characterization in calcified aortic valves may lend insight into the pathogenesis of the disease. Methods: Fourteen calcified aortic valves removed during valve replacement surgery were immunohistochemically stained for the proteoglycans decorin, biglycan, and versican, as well as the glycosaminoglycan hyaluronan. Staining intensity was evaluated in the following regions of interest: center of calcified nodule, edge of nodule, tissue directly surrounding the nodule; center and tissue surrounding small " prenodules"; and fibrosa layer of normal regions of the leaflet distanced from the nodule. Results: Decorin, biglycan, and versican, as well as hyaluronan, were abundantly present immediately surrounding the calcified nodules, but minimally within the nodule itself. Expression of decorin and biglycan in and surrounding prenodules was greater than in the edge and center regions of mature nodules. The levels of expression of the proteoglycans and hyaluronan were highly correlated with one another in the different regions of the valve. Conclusions: The three proteoglycans and hyaluronan demonstrated distinctive localization relative to nodules within calcified aortic valves, where they likely mediate lipid retention, cell proliferation, and extracellular matrix remodeling, and motivate further study. Comparisons between expression of these components in mature nodules and prenodules suggest distinct roles for these components in nodule progression, especially in the tissues surrounding the nodules.