Bailey Emma L, Bazigou Eleni, Sowinski Piotr S J, Weinberg Peter D
Department of Bioengineering, Imperial College London, London, United Kingdom.
PLoS One. 2015 Mar 17;10(3):e0120363. doi: 10.1371/journal.pone.0120363. eCollection 2015.
Uptake of circulating macromolecules by the arterial wall may be a critical step in atherogenesis. Here we investigate the age-related changes in patterns of uptake that occur in the rabbit. In immature aortas, uptake was elevated in a triangle downstream of branch ostia, a region prone to disease in immature rabbits and children. By 16-22 months, uptake was high lateral to ostia, as is lesion prevalence in mature rabbits and young adults. In older rabbits there was a more upstream pattern, similar to the disease distribution in older people. These variations were predominantly caused by the branches themselves, rather than reflecting larger patterns within which the branches happened to be situated (as may occur with patterns of haemodynamic wall shear stress). The narrow streaks of high uptake reported in some previous studies were shown to be post mortem artefacts. Finally, heparin (which interferes with the NO pathway) had no effect on the difference in uptake between regions upstream and downstream of branches in immature rabbits but reversed the difference in older rabbits, as does inhibiting NO synthesis directly. Nevertheless, examination of uptake all around the branch showed that changes occurred at both ages and that they were quite subtle, potentially explaining why inhibiting NO has only minor effects on lesion patterns in mature rabbits and contradicting the earlier conclusion that mechanotransduction pathways change with age. We suggest that recently-established changes in the patterns of haemodynamic forces themselves are more likely to account for the age-dependence of uptake patterns.
动脉壁对循环大分子的摄取可能是动脉粥样硬化形成的关键步骤。在此，我们研究了家兔摄取模式中与年龄相关的变化。在未成熟主动脉中，分支开口下游的一个三角形区域摄取量升高，该区域在未成熟兔和儿童中易患疾病。到16 - 22个月时，开口外侧摄取量较高，这与成熟兔和年轻成年人中的病变发生率一致。在老年兔中，摄取模式更偏向于上游，类似于老年人中的疾病分布。这些变化主要是由分支本身引起的，而不是反映分支所处的更大模式（血流动力学壁面剪应力模式可能会出现这种情况）。先前一些研究报道的高摄取窄条纹被证明是死后假象。最后，肝素（干扰NO途径）对未成熟兔分支上游和下游区域的摄取差异没有影响，但在老年兔中却逆转了这种差异，直接抑制NO合成也有同样效果。然而，对分支周围摄取情况的检查表明，两个年龄段都发生了变化，而且变化相当细微，这可能解释了为什么抑制NO对成熟兔病变模式只有轻微影响，也与早期关于机械转导途径随年龄变化的结论相矛盾。我们认为，最近血流动力学力模式的变化更有可能解释摄取模式的年龄依赖性。
