Moreira-Costa Liliana, Barros António S, Lourenço André P, Leite-Moreira Adelino F, Nogueira-Ferreira Rita, Thongboonkerd Visith, Vitorino Rui
Department of Surgery and Physiology, Cardiovascular R&D Center, Faculty of Medicine of the University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal.
Department of Cardiothoracic Surgery, Centro Hospitalar Universitário São João, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal.
Proteomes. 2021 Feb 1;9(1):8. doi: 10.3390/proteomes9010008.
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.
心血管疾病（CVDs）被广泛认为是全球范围内的主要死亡原因。尽管在过去几十年临床管理方面取得了进展，但其潜在的病理机制在很大程度上仍不清楚。外泌体因其在生理和病理条件下细胞间通讯中的相关性而引起了研究人员的关注。这些囊泡被认为是心血管疾病潜在的补充生物标志物；然而，外泌体在心血管疾病中的作用仍未完全阐明。在此，我们对外泌体的生物发生、特征和功能以及不同的外泌体分离技术进行了文献检索。此外，为了对外泌体与心血管疾病之间的相互作用提供新的见解，我们还对冠状动脉疾病（CAD）和心力衰竭（HF）中外泌体衍生介质的作用进行了网络分析，以整合不同的信息来源。上调的外泌体miRNA miR-133a、miR-208a、miR-1、miR-499-5p和miR-30a被描述用于急性心肌梗死的早期诊断；而外泌体衍生的miR-192、miR-194、miR-146a和miR-92b-5p被认为是心力衰竭发展的潜在生物标志物。在CAD患者中，上调的外泌体蛋白，包括纤维蛋白原β/γ链、α-胰蛋白酶抑制剂重链和α-1抗糜蛋白酶，被评估为假定的蛋白质生物标志物。从CAD患者中下调的蛋白质来看，白蛋白、簇蛋白和维生素D结合蛋白被认为与评估预后相关。Vesiclepedia数据库包括CAD患者中外泌体来源的上调miR-133a以及HF患者中外泌体上调的miR-192、miR-194和miR-146a。此外，Vesiclepedia还包括CAD患者中5种上调和13种下调的外泌体蛋白。未包含的miRNA和蛋白质尚未在外泌体中被鉴定出来，可建议进一步研究。本报告强调需要进一步开展研究，重点关注鉴定和验证外泌体来源的miRNA和蛋白质作为CAD和HF的生物标志物，这将能够利用外泌体生物标志物指导心血管疾病的诊断/预后评估。
