**Conflict of interest**

*Extracellular Vesicles and Their Importance in Human Health*

**6. Progress and challenges in extracellular vesicle field**

EVs vis-à-vis target cells to avoid the possible side effects [126].

ting the heavy millstone of metabolic disease [112].

**7. Conclusions**

are also highlighted.

**Acknowledgements**

Romanian Academy.

Although research into EV field is gaining ground, some challenges need to be overcome before using them in the clinic, such as: (i) optimization of EV isolation procedures, especially the time of protocols, decrease of amount of samples, and the selective isolation of distinct EV subtypes; (ii) the large-scale production in good manufacturing conditions; and (iii) increase of the specificity of engineered

Additionally, much still remains to be revealed regarding the role of EVs in cell-cell communication both in health and diabetic cardiovascular disorders. Specifically, understanding the effects of the chronic inflammatory environment in diabetes on the packaging and release of endothelial-EVs and their following interactions with cardiomyocytes could be useful [112]. Advancing the knowledge regarding the cellular source and destination of EVs in CVDs will allow exploration of the specific cellular interactions, while understanding EV organ-tropism will help to target specific tissues, improving the efficiency of miRNA-based therapies. Even so, with many problems remaining to be resolved, as we mentioned above, prior EV-based therapeutics might be clinically used to treat CVDs. Anywise, the many studies underline their potential as successful therapeutic targets in combat-

Overall, our chapter strongly suggests that EVs may function as significant regulators of both physiological and pathological conditions and demonstrates their universal role in the relationship between diabetes and cardiovascular disease. Their unique properties as biological vectors modulating diabetic cardiovascular diseases, including atherosclerosis, coronary artery disease, and peripheral arterial disease,

Undoubtedly, elucidation of terminology, biogenesis, biological content, and function of EVs contributes to better understanding of the complexity of their role in influencing the different processes affected in diabetic cardiovascular diseases. Consequently, we envisage that for EVs used as clinical biomarkers, therapeutic targets, and biomedical tools in diabetes and associated complications, there is a need for developing a molecular system of EVs based on their lipidomic, metabolomic, and miRnomic signature. Once these issues are clarified, preventative and

Despite the fact that existing literature discussed in this chapter describes the EV importance in diabetic cardiovascular diseases, it also leaves some significant questions unanswered. Thus, it becomes increasingly complicated to establish an EV structure either beneficial or harmful, to clarify their role either good or bad, in both health and disease. Incontestably, more research evaluating such properties is necessary to establish EVs' value as clinical biomarkers, therapeutic targets, and biomedical tools based on concrete scientific results for diabetic cardiovascular disease treatment.

The authors are grateful to the work supported by grants of the Romanian National Authority for Scientific Research, CNCS-UEFISCDI, project no. PN-III-P1-1.2-PCCDI-2017-0527, project no. PN-III-P1-1.2-PCCDI-2017-0797, and by the

therapeutic strategies can be implemented and further developed.

**124**

The authors declare that the research was conducted in the absence of any either commercial or financial relationships that could be construed as a potential conflict of interest.
