Abundance and location of proteoglycans and hyaluronan within normal and myxomatous mitral valves

Abstract

Introduction-Extracellular matrix changes occur in many heart valve pathologies. For example, myxomatous mitral valves are reported to contain excess proteoglycans (PGs) and hyaluronan (HA). However, it is unknown which specific PGs are altered in myxomatous valves. Because PGs perform varied functions in connective tissues, this study was designed to identify and localize three matrixassociated PGs as well as HA and the HA receptor for endocytosis (HARE) within myxomatous and normal mitral valves.Methods-Human mitral posterior leaflets (control n=6−9, myxomatous n=14−21, mean age 61 for all groups) were histochemically stained for PG core proteins, HA, and HARE. Stain intensity was semi-quantitatively graded to determine differences in marker abundance betweennormal and myxomatous valves. The PGs were localized to different regions of the leaflet by correspondence to parallel Movat stained sections Results-The PGs decorin, biglycan and versican were more abundant in myxomatous valves than in normal controls (p<0.03). There was a gender effect on PG presence but no age related trends were observed. HA and HARE were distributed throughout all valves. There was no significant difference in HA between groups, but HARE expression was reduced in myxomatous valves compared to normal controls (p<0.002).Conclusion-Excess decorin, biglycan and versican may be associated with the remodeling of other matrix components in myxomatous mitral valves. Decreased expression of HARE in myxomatous valves suggests that HA metabolism could be altered in myxomatous mitral valve disease. These finding contribute towards elucidating the pathogenesis of myxomatous mitral valve disease and developing potential new therapies.

Clinical and Pathological Features of Degenerative Mitral Valve Disease: Billowing Mitral Leaflet Versus Fibroelastic Deficiency

“…The layered architecture is destroyed and valve thickening and structural fragility are induced, because individual collagen bundles were fragmented, coiled, disrupted, and decreased consistency is derived from the complicated structure. 3,6,[8][9][10] In addition, it has been reported that similar changes are observed in chordal tendineae. [11][12][13] In some cases, there is an identified genetic and congenital defect in the connective tissue, such as in Marfan syndrome.…”

Myocardial Extracellular Matrix

“…Indeed, SLRPs decorin, biglycan, and lumican are ubiquitously expressed in mitral valves. 70,129 After mitral regurgitation, decorin expression increases in mitral valve leaflets, 130 whereas in the left ventricle, decorin and lumican expression decreases. 131 Remodeling of the left ventricle in response to mechanical or hormonal activation leads to changes in the expression of matrix components like these SLRPs.…”

Wnt/β-catenin signaling enables developmental transitions during valvulogenesis

“…In developing cushion/ valve mesenchyme, active Wnt signaling could maintain a progressively restricted pool of undifferentiated mesenchymal cells that produce a growth-supportive Vcan-rich microenvironment and remain responsive to additional developmental cues like FGF. As myxomatous valves are characterized by increased levels of Vcan and other proteoglycans (Gupta et al, 2009), excessive Wnt activity could promote this common manifestation of valve disease. Postnatally, specialized Wnt-responsive valve interstitial cells might serve as a stem-cell reservoir for valve homeostasis and repair.…”