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Effect of cyclic mechanical strain on glycosaminoglycan and proteoglycan synthesis by heart valve cells.

机译:循环机械应变对心脏瓣膜细胞糖胺聚糖和蛋白聚糖合成的影响。

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Heart valves are presumed to remodel their extracellular matrix upon application of mechanical strains. In this study, we investigated the effect of cyclic tensile strain on valvular interstitial cells' synthesis of glycosaminoglycans (GAGs) and proteoglycans (PGs), which are altered during myxomatous degeneration. Interstitial cells were isolated from mitral valve leaflets and chordate, and seeded separately within three-dimensional collagen gels. Cell-seeded collagen gels were then subjected to cyclic strains of 2%, 5% or 10% at 1.16 Hz for 48 h using a custom-built stretching device. The application of cyclic strains reduced the total GAGs retained within collagen gels in a magnitude-dependent manner for both leaflet and chordal cells. With increasing strain magnitude, however, secretion of total GAGs into the medium was reduced for leaflet cells and elevated for chordal cells. Retention of 4-sulfated GAGs increased with increasing strain magnitude for both cell types; for the chordal samples, retention of 6-sulfated GAGs was reduced at higher strain magnitudes. Compared to statically constrained or unconstrained conditions, the application of cyclic strain reduced the secretion of 6-sulfated GAGs by both cell types, and elevated secretion of 4-sulfated GAGs by leaflet cells only. Retention of the PG biglycan and secretion of the PG decorin was significantly reduced at 10% strain compared to 2% strain. In addition, there were numerous differences in the strain-dependent retention and secretion of GAGs and PGS within the leaflet and chordal groups. These results demonstrate that GAG and PG synthesis by VICs is regulated by cyclic stretching conditions.
机译:据推测,在施加机械应变后,心脏瓣膜可重塑其细胞外基质。在这项研究中,我们研究了循环拉伸应变对粘液变性期间改变的糖胺聚糖(GAGs)和蛋白聚糖(PGs)的瓣膜间质细胞合成的影响。从二尖瓣小叶和绒毛膜分离间质细胞,并分别接种在三维胶原凝胶中。然后使用定制的拉伸装置在1.16 Hz下对细胞接种的胶原蛋白凝胶进行2%,5%或10%的循环应变48小时。对于小叶和弦细胞,循环菌株的应用以幅度依赖的方式减少了胶原凝胶中保留的总GAG。然而,随着应变幅度的增加,对于小叶细胞,总GAG向培养基的分泌减少,而对弦细胞则增加。两种细胞类型中,4-硫酸化GAG的保留率均随着应变幅度的增加而增加。对于弦样品,在较高的应变强度下,六硫酸化GAG的保留降低了。与静态约束或非约束条件相比,循环应变的应用减少了两种细胞类型对6-硫酸化GAG的分泌,并且仅由小叶细胞提高了4-硫酸化GAG的分泌。与2%菌株相比,在10%菌株中PG双糖链蛋白的保留和PG核心蛋白聚糖的分泌显着降低。此外,在小叶和弦组中,GAG和PGS的应变依赖性保留和分泌存在许多差异。这些结果表明,VIC合成GAG和PG受循环拉伸条件的调节。

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