Department of Nephrology, Hospital Universitari Bellvitge, and Bellvitge Research Institute (IDIBELL), L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
Independent Researcher, 08950 Barcelona, Spain.
Int J Mol Sci. 2018 Jun 12;19(6):1734. doi: 10.3390/ijms19061734.
Atherosclerosis (ATH) and coronary artery disease (CAD) are chronic inflammatory diseases with an important genetic background; they derive from the cumulative effect of multiple common risk alleles, most of which are located in genomic noncoding regions. These complex diseases behave as nonlinear dynamical systems that show a high dependence on their initial conditions; thus, long-term predictions of disease progression are unreliable. One likely possibility is that the nonlinear nature of ATH could be dependent on nonlinear correlations in the structure of the human genome. In this review, we show how chaos theory analysis has highlighted genomic regions that have shared specific structural constraints, which could have a role in ATH progression. These regions were shown to be enriched with repetitive sequences of the family, genomic parasites that have colonized the human genome, which show a particular secondary structure and are involved in the regulation of gene expression. Here, we show the impact of elements on the mechanisms that regulate gene expression, especially highlighting the molecular mechanisms via which the elements alter the inflammatory response. We devote special attention to their relationship with the long noncoding RNA (lncRNA); antisense noncoding RNA in the locus (), a risk factor for ATH; their role as microRNA (miRNA) sponges; and their ability to interfere with the regulatory circuitry of the (nuclear factor kappa B) NF-κB response. We aim to characterize ATH as a nonlinear dynamic system, in which small initial alterations in the expression of a number of repetitive elements are somehow amplified to reach phenotypic significance.
动脉粥样硬化（ATH）和冠状动脉疾病（CAD）是具有重要遗传背景的慢性炎症性疾病；它们源于多个常见风险等位基因的累积效应，其中大多数位于基因组非编码区域。这些复杂疾病表现为非线性动力系统，对其初始条件有很强的依赖性；因此，疾病进展的长期预测是不可靠的。一种可能的情况是，ATH 的非线性性质可能依赖于人类基因组结构的非线性相关性。在这篇综述中，我们展示了混沌理论分析如何突出了具有共同特定结构约束的基因组区域，这些区域可能在 ATH 进展中起作用。这些区域富含家族的重复序列，这些基因组寄生虫已经在人类基因组中定居，它们具有特定的二级结构，并参与基因表达的调控。在这里，我们展示了 元素对调节基因表达的机制的影响，特别是强调了 元素改变炎症反应的分子机制。我们特别关注它们与长非编码 RNA（lncRNA）的关系；ATH 的风险因素——位于 基因座的反义非编码 RNA（）；它们作为 microRNA（miRNA）海绵的作用；以及它们干扰（核因子 kappa B）NF-κB 反应的调节电路的能力。我们旨在将 ATH 表征为一个非线性动力系统，其中一些重复元素表达的微小初始变化以某种方式被放大，达到表型意义。
