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.
Highlights
Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide [1]
We found that one upregulated miRNA in Coronary artery disease (CAD) and three upregulated miRNAs in heart failure (HF) patients were included in the Vesiclepedia database (Figure 3, Table 3, Table S4 and Table S5)
The network analysis of both miRNAs and proteins of exosomal origin in CAD and HF allowed the identification of possible molecular biomarkers for the diagnosis of these diseases
Summary
Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide [1]. The identification of novel biomarkers that can aid diagnosis and direct therapeutic strategies is a key target to address in order to achieve further reduction of morbidity and mortality rates [3]. Exosomes have been described in numerous cell–cell and cell–environment communications through the release of biological and/or chemical molecules to recipient cells. They govern physiological processes and show typical disturbances, which may constitute mechanistic pathways in various disease processes [6]. The biological content of exosomes, such as proteins and microRNAs (miRNAs), is conditioned by the cellular origin, function, and current state as a fingerprint of the donor cell. Translation to clinically meaningful studies and clinical practice is lacking, mostly due to inconsistent exosomal isolation methods [9]
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