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

Effect of cyclic mechanical strain on glycosaminoglycan and proteoglycan synthesis by heart valve cells.
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DOI:
10.1016/j.actbio.2008.10.009
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发表时间:
2009-02
期刊:
影响因子:
9.7
通讯作者:
Grande-Allen, K. Jane
Grande-Allen, K. Jane
中科院分区:
工程技术1区
文献类型:
--
作者:
Gupta, Vishal;Tseng, Hubert;Lawrence, Brian D.;Grande-Allen, K. Jane

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假定心脏瓣膜在施加机械应变时重塑其细胞外基质。在这项研究中,我们研究了周期性拉伸应变对瓣膜间质细胞合成糖胺聚糖(GAG)和蛋白聚糖(PG)的影响,这些糖胺聚糖和蛋白聚糖在粘液瘤变性过程中发生了变化。从二尖瓣小叶和腱索分离间质细胞,并分别接种在三维胶原凝胶内。然后使用定制的拉伸装置使接种细胞的胶原凝胶在1.16 Hz下经受2%、5%或10%的循环应变48小时。循环应变的应用以幅度依赖性方式减少了瓣叶和腱索细胞中保留在胶原凝胶内的总GAG。然而,随着应变幅度的增加,分泌到培养基中的总糖胺酸减少的小叶细胞和升高的索细胞。对于两种细胞类型,4-硫酸化GAG的保留随着应变幅度的增加而增加;对于腱索样品,6-硫酸化GAG的保留在较高的应变幅度下减少。与静态约束或无约束条件相比,循环应变的应用减少了两种细胞类型的6-硫酸化GAG的分泌,并且仅增加了小叶细胞的4-硫酸化GAG的分泌。与2%菌株相比,PG双糖链聚糖的保留和PG核心蛋白聚糖的分泌在10%菌株下显著降低。此外,在瓣叶和腱索组中,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,通过VIC的GAG和PG合成受环状拉伸条件调节。
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 chordae 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 hours 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.
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