Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

ALUminating the Path of Atherosclerosis Progression: Chaos Theory Suggests a Role for Alu Repeats in the Development of Atherosclerotic Vascular Disease

Version 1 : Received: 31 March 2018 / Approved: 4 April 2018 / Online: 4 April 2018 (06:36:55 CEST)

How to cite: Hueso, M.; Cruzado, J.M.; Torras, J.; Navarro, E. ALUminating the Path of Atherosclerosis Progression: Chaos Theory Suggests a Role for Alu Repeats in the Development of Atherosclerotic Vascular Disease. Preprints 2018, 2018040051. https://doi.org/10.20944/preprints201804.0051.v1 Hueso, M.; Cruzado, J.M.; Torras, J.; Navarro, E. ALUminating the Path of Atherosclerosis Progression: Chaos Theory Suggests a Role for Alu Repeats in the Development of Atherosclerotic Vascular Disease. Preprints 2018, 2018040051. https://doi.org/10.20944/preprints201804.0051.v1

Abstract

Atherosclerosis (ATH) and Coronary Artery Disease (CAD) are chronic inflammatory diseases with an important genetic background which derive from the cumulative effect of multiple common risk alleles, most of them located in genomic non-coding regions. These complex diseases behave as non-linear dynamical systems that show a high dependence on their initial conditions, so that long-term predictions of disease progression are unreliable. One likely possibility is that the non-linear nature of ATH could be dependent on non-linear correlations in the structure of the human genome. In this review we show how Chaos theory analysis highlighted genomic regions that shared specific structural constraints that could have a role in ATH progression. These regions were shown to be enriched in repetitive sequences of the Alu family, genomic parasites which colonized the human genome, which show a particular secondary structure and have been involved in the regulation of gene expression. We also review the impact of Alu elements on the mechanisms that regulate gene expression, especially highlighting the molecular mechanisms by which the Alu elements could alter the inflammatory homeostasis. We devise especial attention to their relationship with the lncRNA ANRIL, the strongest risk factor for ATH, their role as miRNA sponges, and their ability to interfere with the regulatory circuitry of the NF-kB response. We aim to characterize ATH as a non-linear dynamic system in which small initial alterations in the expression of a number of repetitive elements are somehow amplified to reach phenotypic significance.

Keywords

atherosclerosis; cardiovascular disease; chaos theory; non-coding RNAs; Alu-elements; NF-κB; miRNA; miRNA sponges

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

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