microRNAs as biomarkers of risk of major adverse cardiovascular events in atrial fibrillation

Abstract

Atrial fibrillation is a complex and multifactorial disease. Although prophylactic anticoagulation has great benefits in avoiding comorbidities, adverse cardiovascular events still occur and thus in recent decades, many resources have been invested in the identification of useful markers in the prevention of the risk of MACE in these patients. As such, microRNAs, that are small non-coding RNAs whose function is to regulate gene expression post-transcriptionally, have a relevant role in the development of MACE. miRNAs, have been investigated for many years as potential non-invasive biomarkers of several diseases. Different studies have shown their utility in the diagnosis and prognosis of cardiovascular diseases. In particular, some studies have associated the presence of certain miRNAs in plasma with the development of MACE in AF. Despite these results, there are still many efforts to be done to allow the clinical use of miRNAs. The lack of standardization concerning the methodology in purifying and detecting miRNAs, still provides contradictory results. miRNAs also have a functional impact in MACE in AF through the dysregulation of immunothrombosis. Indeed, miRNAs may be a link between MACE and inflammation, through the regulation of neutrophil extracellular traps that are a key element in the establishment and evolution of thrombotic events. The use of miRNAs as therapy against thromboinflammatory processes should also be a future approach to avoid the occurrence of MACE in atrial fibrillation.

miRNAs in Heart Development and Disease

“…Thus, they might be useful molecular markers for monitoring for pregnancy-associated cardiovascular diseases, opening new possibilities for early, non-invasive prenatal diagnosis and thus prevention, as recently reviewed by Omran et al [199]. The identification of microRNAs as suitable biomarkers has also been extensively reported in major adverse cardiovascular events in atrial fibrillation [200], heart failure [201] and arrhythmogenic cardiomyopathies [202], among other cardiovascular diseases. Importantly, their use in prevention, treatment, and management is progressively emerging, although some additional efforts are required before they fully enter the clinical arena, such as, for example, providing adequate standardization for the methodology of purifying and detecting microRNA [200].…”

“…The identification of microRNAs as suitable biomarkers has also been extensively reported in major adverse cardiovascular events in atrial fibrillation [200], heart failure [201] and arrhythmogenic cardiomyopathies [202], among other cardiovascular diseases. Importantly, their use in prevention, treatment, and management is progressively emerging, although some additional efforts are required before they fully enter the clinical arena, such as, for example, providing adequate standardization for the methodology of purifying and detecting microRNA [200]. Nonetheless, the path to use microRNAs for the treatment of cardiovascular diseases is promising as clinical trials in other disease contexts have also been successful [203] and the first approaches are already in the way for heart failure [204].…”

Principles and Limitations of miRNA Purification and Analysis in Whole Blood Collected during Ablation Procedure from Patients with Atrial Fibrillation

“…miRNA can also play an important role as predictors of coronary vascular disease in patients with AF. A study conducted by Reyes-Garcia et al showed that patients with highly increased risks of a major adverse cardiovascular event had significantly higher levels of miR-22-3p and miR-107 and lower levels of miR-146a-5p [24]. miRNA also have an important role in vascular health and atherosclerotic processes.…”

No Detectable Differences in microRNA Plasma Levels between Diabetic Hypertensive Patients with and without Incident Subclinical Atrial Fibrillation

“…Although miRNAs may appear as attractive, new biomarkers for predicting AFmonitoring AF treatment effects, predicting major adverse events in AF patients, or characterizing the underlying mechanism of the development and progression of AF [26,27,[30][31][32][33][34]43]-there are several factors currently limiting their use in daily clinical practice. A major problem is the lack of standardization of the miRNA analysis process, from obtaining the RNA over the purification of the material to the measurement including the normalization of the measured miRNA levels, which has impact on the results and makes them difficult to compare [26,27,[30][31][32][33][34].…”