Publication:
New Biomarkers for Atherothrombosis in Antiphospholipid Syndrome: Genomics and Epigenetics Approaches.

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Date

2019-04-16

Authors

Lopez-Pedrera, Chary
Barbarroja, Nuria
Patiño-Trives, Alejandra Mª
Collantes, Eduardo
Aguirre, Mª Angeles
Perez-Sanchez, Carlos

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Frontiers Research Foundation
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Abstract

Antiphospholipid Syndrome (APS) is an autoimmune disorder, characterized by pregnancy morbidity and/or a hyper coagulable state involving the venous or the arterial vasculature and associated with antiphospholipid antibodies (aPL), including anti-cardiolipin antibodies (aCL), anti-beta2-glycoprotein I (anti-ß2GPI), and Lupus anticoagulant (LA). In recent years there have been many advances in the understanding of the molecular basis of vascular involvement in APS. APS is of multifactorial origin and develops in genetically predisposed individuals. The susceptibility is determined by major histocompatibility complex (MHC). Different HLA-DR and HLA-DQ alleles have been reported in association with APS. Moreover, MHC II alleles may determine the autoantibody profile and, as such, the clinical phenotype of this disease. Besides, polymorphisms in genes related to the vascular system are considered relevant factors predisposing to clinical manifestations. Antiphospholipid antibodies (aPL) induce genomic and epigenetic alterations that support a pro- thrombotic state. Thus, a specific gene profile has been identified in monocytes from APS patients -related to aPL titres in vivo and promoted in vitro by aPL- explaining their cardiovascular involvement. Regarding epigenetic approaches, we previously recognized two miRNAs (miR-19b/miR-20a) as potential modulators of tissue factor, the main receptor involved in thrombosis development in APS. aPLs can further promote changes in the expression of miRNA biogenesis proteins in leukocytes of APS patients, which are translated into an altered miRNA profile and, consequently, in the altered expression of their protein targets related to thrombosis and atherosclerosis. MicroRNAs are further released into the circulation, acting as intercellular communicators. Accordingly, a specific signature of circulating miRNAs has been recently identified in APS patients as potential biomarkers of clinical features. Genomics and epigenetic biomarkers might also serve as indices for disease progression, clinical pharmacology, or safety, so that they might be used to individually predict disease outcome and guide therapeutic decisions. In that way, in the setting of a clinical trial, novel and specific microRNA-mRNA regulatory networks in APS, modified by effect of Ubiquinol treatment, have been identified. In this review, current and previous studies analyzing genomic/epigenetic changes related to the clinical profile of APS patients, and their modulation by effect of specific therapies, are discussed.

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MeSH Terms

Antibodies, Antiphospholipid
Antiphospholipid Syndrome
Atherosclerosis
Biomarkers
DNA Methylation
Epigenesis, Genetic
Extracellular Traps
Gene Expression Profiling
Genetic Markers
Genetic Predisposition to Disease
Genomics
Humans
MicroRNAs
Oxidative Stress
Thrombosis

DeCS Terms

Anticuerpos antifosfolipidos
Aterosclerosis
Epigenesis genetica
Estres oxidativo
Predisposicion genetica a la enfermedad
Sindrome antifosfolipido
Marcadores geneticos
Genomica

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Keywords

Antiphospholipid Syndrome, Cardiovascular disease, Genomics, MicroRNAs, Therapy

Citation

Lopez-Pedrera C, Barbarroja N, Patiño-Trives AM, Collantes E, Aguirre MA, Perez-Sanchez C. New Biomarkers for Atherothrombosis in Antiphospholipid Syndrome: Genomics and Epigenetics Approaches. Front Immunol. 2019 Apr 16;10:764