Integrated mRNA and microRNA Transcriptomes of Monocytes from Antiphospholipid Syndrome Patients Identifies Molecular Networks Related to Their Atherothrombotic Status. Modulatory Effects of In Vivo Ubiquinol Supplementation

Carlos Perez-Sanchez¹, Laura Pérez Sánchez², Alejandra Maria Patiño-Trives³, María Luque Tevar³, Luca Scudeler⁴, Alejandro Ibáñez-Costa³, Patricia Ruiz-Limon⁵, Yolanda Jiménez-Gómez¹, Ivan Arias de la Rosa⁶, Maria Carmen Abalos-Aguilera⁶, Pedro Segui⁷, Nuria Barbarroja¹, Jose Manuel Villalba⁸, Eduardo Collantes Estevez³, Maria Jose Cuadrado⁹, Maria Ángeles Aguirre Zamorano¹ and Chary Lopez-Pedrera³, ¹Rheumatology service, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain, ²IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Spain, ³IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain, ⁴Università degli Studi di Torino, Turin, Italy, ⁵Research Group of Endocrine Diseases, Research Laboratory. Biomedical Research Institute of Malaga (IBIMA).Virgen de la Victoria Universitary Hospital, Malaga, Spain., Málaga, MA, Spain, ⁶Rheumatology Service, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain, ⁷Radiology, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain, ⁸Departamento de Biologia Celular, Fisiologia e Inmunología, University of Córdoba, Cordoba, Spain, ⁹Clinica Universidad de Navarra, Madrid, Spain

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: antiphospholipid syndrome, Cardiovascular disease, epigenetics and monocytes, Gene Expression

Session Information

Date: Sunday, October 21, 2018

Title: 3S079 ACR Abstract: Antiphospholipid Syndrome (851–856)

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: 1. To characterize the mRNAs and microRNAs transcriptomes of monocytes, key immune cells in the atherothrombotic pathology of Antiphospholipid Syndrome patients (APS). 2. To evaluate the role of antiphospholipid antibodies (aPL) in the regulation of these processes. 3. To investigate the short-term effects of in vivo ubiquinol (reduced coenzyme Q10 [Qred]) supplementation.

Methods: Monocytes from peripheral blood of 30 APS patients and 30 healthy donors were purified by negative immunomagnetic selection. Then, gene expression microarray (Agilent G4112F platform) and nCounter microRNA expression arrays (Nanostring) were performed. Functional categorization of altered genes and miRNAs was made using IPA software, and interaction networks were identified. Genes and miRNAs integrating the networks were validated in the whole APS cohort, as well as on a set of thrombotic non-autoimmune patients. Predicted miRNA-mRNA interactions were tested by microRNA over-expression experiments. The short-term effects of in vivo Qred supplementation on the monocyte transcriptomes profiles were further analyzed.

Results: Microarray identified 518 altered genes in APS monocytes. Relevant biofunctions on which these genes were involved included hematological and cardiovascular system development and function, inflammatory response, and embryonic development, among others. Gene alterations were validated in the whole cohort, demonstrated to be stable along the time, divergent of the gene profile in monocytes from non-autoimmune thrombotic patients, and associated to clinical parameters, including thrombotic recurrences and early atherosclerosis. Analysis of miRNA profiles showed altered expression of 22 miRNAs in APS monocytes. Fifty-four genes were inversely correlated and predicted as CVD-related target genes of 19 differentially expressed miRNAs. Association of these genes and miRNAs with the occurrence and type of thrombotic events, obstetric complications and presence of atheroma plaques were demonstrated. Transfection studies further confirmed the relationship between specific miRNAs and their identified target genes. In vitro studies demonstrated the specific modulation of several genes/miRNAs by aPLs. In vivo Qred supplementation of APS patients reversed the monocytes’ altered gene/miRNA profiles.

Conclusion: 1. Gene and microRNA expression profiles allowed the identification of relevant genes and pathways altered in monocytes of APS patients, associated with the pathogenesis of the disease and modulated, at least partially, by aPLs. 2. Specific microRNA-miRNA regulatory networks control the biological processes and factors related to the CV pathology in APS and are modified by in vivo Qred supplementation.

Funded by ISCIII, PI15/01333 and RIER RD16/0012/0015 co-funded with FEDER

Disclosure: C. Perez-Sanchez, None; L. Pérez Sánchez, None; A. M. Patiño-Trives, None; M. Luque Tevar, None; L. Scudeler, None; A. Ibáñez-Costa, None; P. Ruiz-Limon, None; Y. Jiménez-Gómez, None; I. Arias de la Rosa, None; M. C. Abalos-Aguilera, None; P. Segui, None; N. Barbarroja, None; J. M. Villalba, None; E. Collantes Estevez, None; M. J. Cuadrado, None; M. Á. Aguirre Zamorano, None; C. Lopez-Pedrera, None.

To cite this abstract in AMA style:

Perez-Sanchez C, Pérez Sánchez L, Patiño-Trives AM, Luque Tevar M, Scudeler L, Ibáñez-Costa A, Ruiz-Limon P, Jiménez-Gómez Y, Arias de la Rosa I, Abalos-Aguilera MC, Segui P, Barbarroja N, Villalba JM, Collantes Estevez E, Cuadrado MJ, Aguirre Zamorano MÁ, Lopez-Pedrera C. Integrated mRNA and microRNA Transcriptomes of Monocytes from Antiphospholipid Syndrome Patients Identifies Molecular Networks Related to Their Atherothrombotic Status. Modulatory Effects of In Vivo Ubiquinol Supplementation [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/integrated-mrna-and-microrna-transcriptomes-of-monocytes-from-antiphospholipid-syndrome-patients-identifies-molecular-networks-related-to-their-atherothrombotic-status-modulatory-effects-of-in-vivo-u/. Accessed .

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