Intracellular Ca(2+) accumulation is strain-dependent and correlates with apoptosis in aortic valve fibroblasts.
Intracellular Ca(2+) accumulation is strain-dependent and correlates with apoptosis in aortic valve fibroblasts.
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DOI：
10.1016/j.jbiomech.2011.11.031
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发表时间：
2012-03-15
影响因子：
2.4
通讯作者：
Merryman WD
中科院分区：
文献类型：
--
作者：
Hutcheson JD;Venkataraman R;Baudenbacher FJ;Merryman WD
主动脉瓣（AV）疾病的特征通常是在AV瓣叶内形成钙化结节，改变功能生物力学。在体外，这些结节的形成与成骨分化和/或AV间质细胞（AVIC）的收缩和凋亡增加有关，导致磷酸钙晶体结构的生长。在其他几种细胞类型中，细胞内Ca 2+增加已被证明是成骨分化激活的重要组成部分。然而，已知升高的细胞内Ca 2+介导细胞收缩，并且还显示在许多细胞类型中导致细胞凋亡。因此，细胞内Ca 2+的升高可能先于导致钙化的细胞变化，并且已显示与AVIC类似的成纤维细胞响应于机械应变而表现出细胞内Ca 2+的增加。在这项研究中，我们假设应变诱导细胞内钙离子积累通过牵张激活的钙通道。我们也有兴趣在评估可能的相关性细胞内Ca 2+的增加和凋亡的AVIC。为了验证我们的假设，培养的猪AVIC被用来评估应变，细胞内Ca 2+和细胞凋亡之间的相关性。Ca 2+敏感的荧光染料被用来测量实时细胞内Ca 2+的变化，应变AVICs。然后用流式细胞仪Annexin V凋亡测定将Ca 2+变化与AVIC凋亡相关。这些数据表明，细胞内Ca 2+的应变依赖性积累与AVIC中的细胞凋亡相关。我们认为这些发现提示早期机械传导事件可能启动房室钙化通路。
Aortic valve (AV) disease is often characterized by the formation of calcific nodules within AV leaflets that alter functional biomechanics. In vitro, formation of these nodules is associated with osteogenic differentiation and/or increased contraction and apoptosis of AV interstitial cells (AVICs), leading to growth of calcium phosphate crystal structures. In several other cell types, increased intracellular Ca2+ has been shown to be an important part in activation of osteogenic differentiability. However, elevated intracellular Ca2+ is known to mediate cell contraction, and has also been shown to lead to apoptosis in many cell types. Therefore, a rise in intracellular Ca2+ may precede cellular changes that lead to calcification, and fibroblasts similar to AVICs have been shown to exhibit increases in intracellular Ca2+ in response to mechanical strain. In this study, we hypothesized that strain induces intracellular Ca2+ accumulation through stretch-activated calcium channels. We were also interested in assessing possible correlations between intracellular Ca2+ increases and apoptosis in AVICs. To test our hypothesis, cultured porcine AVICs were used to assess correlates between strain, intracellular Ca2+, and apoptosis. Ca2+ sensitive fluorescent dyes were utilized to measure real-time intracellular Ca2+ changes in strained AVICs. Ca2+ changes were then correlated with AVIC apoptosis using flow cytometric Annexin V apoptosis assays. These data indicate that strain-dependent accumulation of intracellular Ca2+ is correlated with apoptosis in AVICs. We believe that these findings indicate early mechanotransductive events that may initiate AV calcification pathways.
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影响因子：
14
作者：
Wipff, Pierre-Jean;Majd, Hicham;Hinz, Boris
通讯作者：
Hinz, Boris
DOI：
10.1115/1.2801670
发表时间：
2007-12-01
影响因子：
1.7
作者：
Huang, Hsiao-Ying Shadow;Liao, Jun;Sacks, Michael S.
通讯作者：
Sacks, Michael S.
影响因子：
--
作者：
Merryman, W. David;Liao, Jun;Sacks, Michael S.
通讯作者：
Sacks, Michael S.
影响因子：
2.4
作者：
Merryman, WD;Huang, HYS;Sacks, MS
通讯作者：
Sacks, MS
影响因子：
3.7
作者：
Merryman, W. David;Lukoff, Howard D.;Sacks, Michael S.
通讯作者：
Sacks, Michael S.