Insights into the Diagnostic Potential of Extracellular Vesicles and Their miRNA Signature from Liquid Biopsy as Early Biomarkers of Diabetic Micro/Macrovascular Complications

Abstract

Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. Almost all cell types release EVs, thus they are naturally present in all body fluids. Among the several potential applications, EVs could be used as drug delivery vehicles in disease treatment, in immune therapy because of their immunomodulatory properties and in regenerative medicine. In addition to general markers, EVs are characterized by the presence of specific biomarkers (proteins and miRNAs) that allow the identification of their cell or tissue origin. For these features, they represent a potential powerful diagnostic tool to monitor state and progression of specific diseases. A large body of studies supports the idea that endothelial derived (EMPs) together with platelet-derived microparticles (PMPs) are deeply involved in the pathogenesis of diseases characterized by micro- and macrovascular damages, including diabetes. Existing literature suggests that the detection of circulating EMPs and PMPs and their specific miRNA profile may represent a very useful non-invasive signature to achieve information on the onset of peculiar disease manifestations. In this review, we discuss the possible utility of EVs in the early diagnosis of diabetes-associated microvascular complications, specifically related to kidney.

Extracellular vesicles in metabolic disease

“…Patient plasma and urine are rich sources of EVs and studies have demonstrated EV miRNAs as diagnostic tools in individuals suffering from metabolic [2–4, 9] and cardiovascular disease [22, 23]. A recent meta-analysis by Li et al [24] reported that levels of EVs of platelet, endothelial cell and monocyte origin were significantly raised in individuals with type 2 diabetes from 48 independent studies [24, 25].…”

Nano-Vesicle (Mis)Communication in Senescence-Related Pathologies

“…Several studies have conferred a supporting role for EVs in various diseases and could assist as diagnostic tools. The modulation of senescent cells, senescence-associated factors, and senescent EVs seems to be a promising strategy for mitigating age-related diseases [ 99 ]. Salient features of exosomes from young and aged individuals are explained in Table 1 and graphically represented in Figure 3 .…”

Insights into the Role of MicroRNAs in the Onset and Development of Diabetic Neuropathy

“…Therefore, circulating miRNAs have been already considered as predictive biomarkers for aging [30], cancer [29], and neurological disorders such as Alzheimer’s disease (AD) [31], multiple sclerosis [32], Parkinson’s disease (PD) [33], and epilepsy [34]. In addition, miRNAs have been also proposed as potential biomarkers for diabetes and its vascular complications [35]. Indeed, alterations of specific miRNA levels can lead not only to the development of chronic inflammation observed in diabetic patients but also to β-cell loss/dysfunction and dysregulation of insulin secretion and signaling along with insulin-resistance and its chronic complications [36].…”