Exosome-Derived Mediators as Potential Biomarkers for Cardiovascular Diseases: A Network Approach

Abstract

Cardiovascular diseases (CVDs) are widely recognized as the leading cause of mortality worldwide. Despite the advances in clinical management over the past decades, the underlying pathological mechanisms remain largely unknown. Exosomes have drawn the attention of researchers for their relevance in intercellular communication under both physiological and pathological conditions. These vesicles are suggested as complementary prospective biomarkers of CVDs; however, the role of exosomes in CVDs is still not fully elucidated. Here, we performed a literature search on exosomal biogenesis, characteristics, and functions, as well as the different available exosomal isolation techniques. Moreover, aiming to give new insights into the interaction between exosomes and CVDs, network analysis on the role of exosome-derived mediators in coronary artery disease (CAD) and heart failure (HF) was also performed to incorporate the different sources of information. The upregulated exosomal miRNAs miR-133a, miR-208a, miR-1, miR-499-5p, and miR-30a were described for the early diagnosis of acute myocardial infarction, while the exosome-derived miR-192, miR-194, miR-146a, and miR-92b-5p were considered as potential biomarkers for HF development. In CAD patients, upregulated exosomal proteins, including fibrinogen beta/gamma chain, inter-alpha-trypsin inhibitor heavy chain, and alpha-1 antichymotrypsin, were assessed as putative protein biomarkers. From downregulated proteins in CAD patients, albumin, clusterin, and vitamin D-binding protein were considered relevant to assess prognosis. The Vesiclepedia database included miR-133a of exosomal origin upregulated in patients with CAD and the exosomal miR-192, miR-194, and miR-146a upregulated in patients with HF. Additionally, Vesiclepedia included 5 upregulated and 13 downregulated exosomal proteins in patients in CAD. The non-included miRNAs and proteins have not yet been identified in exosomes and can be proposed for further research. This report highlights the need for further studies focusing on the identification and validation of miRNAs and proteins of exosomal origin as biomarkers of CAD and HF, which will enable, using exosomal biomarkers, the guiding of diagnosis/prognosis in CVDs.

Association between Exosomal miRNAs and Coronary Artery Disease by Next-Generation Sequencing

“…Notably, Moreira-Costa et al performed a literature search and network analysis to evaluate the interaction between exosomes and cardiovascular diseases [ 21 ]. For CAD patients, up-regulated exosomal proteins, including fibrinogen beta/gamma chain, inter-alpha-trypsin inhibitor heavy chain, and alpha-1 antichymotrypsin, were assessed as putative protein biomarkers.…”

“…For CAD patients, up-regulated exosomal proteins, including fibrinogen beta/gamma chain, inter-alpha-trypsin inhibitor heavy chain, and alpha-1 antichymotrypsin, were assessed as putative protein biomarkers. Several down-regulated proteins were also considered relevant to CAD, such as albumin, clusterin, and vitamin-D-binding protein [ 21 ]. While our findings provide essential information for the involvement of exosomal miRNAs in stable three-vessel CAD, their results shed light on the possible validation of miRNAs and exosome-originated protein in combination with the novel biomarkers of CAD [ 21 ].…”

Traditional and Emerging Biomarkers in Asymptomatic Left Ventricular Dysfunction—Promising Non-Coding RNAs and Exosomes as Biomarkers in Early Phases of Cardiac Damage

“…On the contrary, even though its role in HF is still unknown and it is upregulated in patients with HF, exo-miRNA-92a has been proposed as a clinical biomarker because of its upregulation in patients with HF, high sensitivity/sensibility, and correlation with echocardiographic indices for LV dilation and dysfunction [ 82 ]. It is noteworthy that a recent study calls into question the exosomal origin of miRNA-92a, warranting further investigations [ 83 ]. Overall, the confirmation of miRNAs presence in exosomes together with the knowledge of their function in HF pathogenesis are emerging as important starting points for the clinical translation of exo-miRNAs.…”

MicroRNAs and Calcium Signaling in Heart Disease

“…Another study found that pharmacological inhibition of miR-146a via antagomir injection attenuated cardiac dysfunction and inhibited cardiac remodeling in rats with MI-induced HF [ 87 ]. Previous studies have shown that miR-146a can be used as a potential biomarker to evaluate the efficacy of anti-HF agents [ 88 ].…”