Role of microRNAs in the Development of Cardiovascular Disease in Systemic Autoimmune Disorders

Abstract

Rheumatoid Arthritis (RA), Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are the systemic autoimmune diseases (SADs) most associated with an increased risk of developing cardiovascular (CV) events. Cardiovascular disease (CVD) in SADs results from a complex interaction between traditional CV-risk factors, immune deregulation and disease activity. Oxidative stress, dyslipidemia, endothelial dysfunction, inflammatory/prothrombotic mediators (cytokines/chemokines, adipokines, proteases, adhesion-receptors, NETosis-derived-products, and intracellular-signaling molecules) have been implicated in these vascular pathologies. Genetic and genomic analyses further allowed the identification of signatures explaining the pro-atherothrombotic profiles in RA, SLE and APS. However, gene modulation has left significant gaps in our understanding of CV co-morbidities in SADs. MicroRNAs (miRNAs) are emerging as key post-transcriptional regulators of a suite of signaling pathways and pathophysiological effects. Abnormalities in high number of miRNA and their associated functions have been described in several SADs, suggesting their involvement in the development of atherosclerosis and thrombosis in the setting of RA, SLE and APS. This review focusses on recent insights into the potential role of miRNAs both, as clinical biomarkers of atherosclerosis and thrombosis in SADs, and as therapeutic targets in the regulation of the most influential processes that govern those disorders, highlighting the potential diagnostic and therapeutic properties of miRNAs in the management of CVD.

Regulatory Non-Coding RNAs in Familial Hypercholesterolemia, Theranostic Applications

“…One class of miRNAs biosynthesized in these non-canonical pathways are miRtrons that are derived from introns. Due to the short length of a hairpin structure, after splicing in the nucleus and export to the cytoplasm, processes of pre-miRNA are done by Dicer instead of Drosha and DGCR8 ( Lopez-Pedrera et al, 2020 ). Despite Dicer dependent-pathway, some miRNA are synthesized in a Dicer-independent manner.…”

Unraveling the Association Between Myocardial Infarction of Nonobstructive Coronary Arteries and Anti-phospholipid Syndrome

“…Anti2GPI has the strongest correlation with the pathogenicity of the various plasma proteins antibody ligands in APS (Figure 3) [33][34][35]. Platelets, monocytes, and endothelial cells are stimulated, triggering the expression of tissue factor (TF, the primary inducer of coagulation in vivo), protease-activated receptors (PARs), and proinflammatory cytokines, a mechanism that ultimately results in thrombus [36,37].…”

“…In addition, APLs foster oxidative and mitochondrial dysfunction, which induces an inflammatory profile with increased levels of many cytokines, chemokines, and endothelial damage promoters [36,38].…”

Promising Roles of Exosomal microRNAs in Systemic Lupus Erythematosus

“…MicroRNAs (miRNAs) are a class of small non-coding RNA (about 22 nucleotides) that play a critical role in the regulation of diverse biological processes. Altered miRNA profile is closely associated with progression or remission of SLE (5)(6)(7). miRNAs are not only localized within the cell but presence in various biological fluids.…”