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ALUminating the Path of Atherosclerosis Progression: Chaos Theory Suggests a Role for Alu Repeats in the Development of Atherosclerotic Vascular Disease
- Source :
- Dipòsit Digital de la UB, Universidad de Barcelona, International Journal of Molecular Sciences, Vol 19, Iss 6, p 1734 (2018), International Journal of Molecular Sciences
- Publication Year :
- 2018
- Publisher :
- MDPI, 2018.
-
Abstract
- 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 Alu 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 Alu elements on the mechanisms that regulate gene expression, especially highlighting the molecular mechanisms via which the Alu elements alter the inflammatory response. We devote special attention to their relationship with the long noncoding RNA (lncRNA); antisense noncoding RNA in the INK4 locus (ANRIL), 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.
- Subjects :
- 0301 basic medicine
Alu element
miRNA sponge
Locus (genetics)
Computational biology
Review
Biology
Malalties coronàries
Catalysis
Chaos Game Representation
NF-κB
Inorganic Chemistry
Alu repeats
lcsh:Chemistry
03 medical and health sciences
Coronary diseases
Gene expression
microRNA
ANRIL
Physical and Theoretical Chemistry
Molecular Biology
noncoding RNAs
lcsh:QH301-705.5
Spectroscopy
miRNA
Regulation of gene expression
long-range correlations
Malalties cardiovasculars
Organic Chemistry
General Medicine
Non-coding RNA
Long non-coding RNA
Computer Science Applications
030104 developmental biology
Cardiovascular diseases
lcsh:Biology (General)
lcsh:QD1-999
Human genome
chaos theory
atherosclerosis
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Dipòsit Digital de la UB, Universidad de Barcelona, International Journal of Molecular Sciences, Vol 19, Iss 6, p 1734 (2018), International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....af1685c5d8bf44ba6c0313984aa7f482