Background/Purpose: The interplay between miRNAs and their mRNA targets might constitute an important mechanism in the regulation of the proatherothrombotic status of SLE and APS patients. Aim: To investigate the contribution of deregulated miRNAs to the altered gene profile associated to cardiovascular disease (CVD) in SLE and APS.

Methods: Thirty-three SLE patients, 23 APS patients, and 27 healthy donors were included in the study. Gene Expression Microarray (44K, Agilent, one colour) and nCounter microRNA Expression Arrays (NanoString Technologies) were performed, respectively, to analyze mRNA and miRNA expression profiles on isolated monocytes. Target genes of the differentially expressed miRNAs and interaction networks were identified by using the Ingenuity Pathway Analysis Software (IPA). The resulting identified interactions were validated by RT-PCR on the whole cohorts of SLE and APS patients. The predicted miRNA-mRNA interactions were also tested by functional analyses using microRNA over expression experiments in monocytes purified from SLE and APS patients.

Results:  Comparative analysis of the mRNA profiles showed significantly different expressions of 1222 genes in SLE and 519 genes in APS monocytes in relation to healthy monocytes. Functional analysis by using IPA showed that about 30% of altered genes were involved in inflammation and cardiovascular disease (CVD). Comparative analysis of the microRNA profiles showed significantly different expressions of 37 miRNAs in SLE and 22 miRNAs in APS monocytes. Functional IPA analysis showed that microRNAs altered were mainly related to connective tissue disorders, inflammatory response and reproductive system disease in both autoimmune conditions. In SLE, a total of 63 genes were inversely correlated, and predicted as CVD-related target genes of 23 differentially expressed microRNAs. In APS, a total of 56 genes were inversely correlated, and predicted as CVD-related target genes of 19 differentially expressed miRNAs. Interaction networks of those genes and some microRNAs differentially expressed in SLE and APS monocytes were also identified and showed to be specific of each autoimmune disease. Among them, the overexpression of STAT3, PPARg and CMKLR1 associated to inhibition of miR-130a and miR-149 were verified in SLE patients. In APS patients the overexpression of IL-1A, LDLR, TGF-b, VCAM, VEGF-A and STAT-1 were associated with inhibition of miR-199, miR-30 and miR-145. The expression of these genes and miRNAs correlated with specific parameters related to inflammation, oxidative stress and thrombosis in each autoimmune disease. Moreover, association of these genes and miRNAs with the occurrence and type of thrombotic events, obstetric complications and presence of pathologic CMIT were demonstrated. Transfection studies further confirmed the relationship between these identified target genes and specific miRNAs in both autoimmune disorders.

Conclusion:  We have identified novel and specific microRNA-mRNA regulatory networks related to CVD in SLE and APS patients, thus delineating novel genetic controls of the diverse biological processes and factors related to the cardiovascular pathology present in these autoimmune conditions. Supported by FIS (PI01333/2015) and CTS-7940. Disclosure of Interest: None declared

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/integrated-analysis-of-microrna-and-mrna-expression-profiles-related-to-cardiovascular-disease-in-monocytes-from-systemic-lupus-erythematosus-and-primary-antiphospholipid-syndrome-patients/