Mitral valvular interstitial cell responses to substrate stiffness depend on age and anatomic region.
Mitral valvular interstitial cell responses to substrate stiffness depend on age and anatomic region.
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二尖瓣间质细胞对基底硬度的反应取决于年龄和解剖区域。
DOI：
10.1016/j.actbio.2010.07.001
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发表时间：
2011
影响因子：
9.7
通讯作者：
Grande-Allen,KJane
中科院分区：
文献类型：
--
作者：
Stephens,ElizabethH;Durst,ChristopherA;West,JenniferL;Grande-Allen,KJane
心脏瓣膜的材料特性取决于受试者的年龄、疾病状态和复杂的瓣膜微结构。此外，瓣膜间质细胞（VIC）是机械敏感的，它们合成的细胞外基质不仅决定了瓣膜的材料特性，而且为VIC提供了粘附基质。然而，基质硬度和维克表型和合成性能之间的相互关系知之甚少。鉴于VIC周围的局部机械环境（基底硬度）在不同年龄组和瓣膜的不同解剖区域之间存在差异，假设VIC对基底硬度可能存在年龄和瓣膜区域特定的反应。因此，将来自二尖瓣前叶（MVAC）和后叶（PML）中心的6周龄、6月龄和6岁猪VIC接种到不同硬度的聚乙二醇水凝胶上，并对维克活化（平滑肌α-肌动蛋白（SMaA））和胶原蛋白合成（热休克蛋白-47（HSP 47）、脯氨酰4-羟化酶（P4 H））标记物进行染色。6周龄MVAC在较硬凝胶上表现出SMaA、P4 H和HSP 47降低，而6周龄PML仅表现出HSP 47降低。6个月大的MVAC在底物之间没有差异，而6个月大的PML表现出SMaA、P4 H和HSP 47的降低。6岁MVAC表现出P4 H和HSP 47降低，而6岁PML表现出P4 H降低和HSP 47升高。总之，VIC对基底硬度的年龄特异性和瓣膜区域特异性反应将维克表型与VIC所在的瓣叶区域基质联系起来。这些数据为研究基底硬度在病变和组织工程瓣膜内维克重塑中的作用提供了进一步的依据。
The material properties of heart valves depend on the subject’s age, the state of the disease and the complex valvular microarchitecture. Furthermore, valvular interstitial cells (VICs) are mechanosensitive, and their synthesis of extracellular matrix not only determines the valve’s material properties but also provides an adhesive substrate for VICs. However, the interrelationship between substrate stiffness and VIC phenotype and synthetic properties is poorly understood. Given that the local mechanical environment (substrate stiffness) surrounding VICs differs among different age groups and different anatomic regions of the valve, it was hypothesized that there may be an age- and valve-region-specific response of VICs to substrate stiffness. Therefore, 6-week-, 6-month- and 6-year-old porcine VICs from the center of the mitral valve anterior leaflet (MVAC) and posterior leaflet (PML) were seeded onto poly(ethylene) glycol hydrogels of different stiffnesses and stained for markers of VIC activation (smooth muscle alpha-actin (SMaA)) and collagen synthesis (heat shock protein-47 (HSP47), prolyl 4-hydroxylase (P4H)). Six-week-old MVAC demonstrated decreased SMaA, P4H and HSP47 on stiffer gels, while 6-week-old PML only demonstrated decreased HSP47. Six-month-old MVAC demonstrated no difference between substrates, while 6-month-old PML demonstrated decreased SMaA, P4H and HSP47. Six-year-old MVAC demonstrated decreased P4H and HSP47, while 6-year-old PML demonstrated decreased P4H and increased HSP47. In conclusion, the age-specific and valve-region-specific responses of VICs to substrate stiffness link VIC phenotype to the leaflet regional matrix in which the VICs reside. These data provide further rationale for investigating the role of substrate stiffness in VIC remodeling within diseased and tissue engineered valves.