Circulating exosomal microRNAs as emerging non‐invasive clinical biomarkers in heart failure: Mega bio‐roles of a nano bio‐particle

Abstract

Exosomes are nano-sized extracellular vesicles containing a cell-specific biologically active cargo of proteins and genetic materials. Exosomes are constitutively released from almost all cell-types and affect neighboring or distant cells through a complex intercellular exchange of the genetic information and/or regulation of certain gene expressions that change the function and behavior of recipient cells. Those released into body fluids are the major mediators of intercellular communications. The success of the biological functions of exosomes is highly mediated by the effective transfer of microRNAs (miRs). Exosomes secreted by a damaged or diseased heart can exhibit alterations in the miRs' profile that may reflect the cellular origin and (patho)physiological state, as a "signature" or "fingerprint" of the donor cell. It has been shown that the transportation of cardiac-specific miRs in exosomes can be rapidly detected and measured, holding great potential as biomarkers in heart diseases. Currently, the search for new biomarkers of heart diseases remains a large and increasing enterprise. Notably, circulating exosomal miRs (Exo-miRs) have successfully gained huge interests for their diagnostic and prognostic potentials. The present review highlights circulating Exo-miRs explored for diagnosis/prognosis and outcome prediction in patients with heart failure (HF). To this end, we explain the feasibility of exosomes as clinical biomarkers, discuss the priority of circulating Exo-miRs over non-exosomal ones as a biomarker, and then outline reported circulating Exo-miRs having the biomarker function in HF patients, together with their mechanism of action. In conclusion, circulating Exo-miRs represent emerging diagnostic (Exo-miR-92b-5p, Exo-miR-146a, Exo-miR-181c, and Exo-miR-495) and prognostic (Exo-miR-192, Exo-miR-194, Exo-miR-34a, Exo-miR-425, Exo-miR-744) biomarkers for HF.

Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1

“…The composition of exosomal cargo is very diverse and includes a wide range of immunosuppressive and immunostimulatory proteins, chemokines, cytokines, cellular receptors, lipids, as well as different nucleic acids such as micro-RNAs and circular RNAs. [62][63][64] Tumor cells can actively produce large levels of exosomes enriched in cancer-promoting cellular contents, such as immunosuppressive proteins like PD-L1, mRNAs, and micro-RNAs, that participate in cancer development and metastasis, through dysregulating antitumor or protumor immunity responses and promoting drug resistance. [65][66][67] Of note, tumor-secreted exosomes contain PD-L1 presented both on the surface and within exosome particles.…”

Extracellular Vesicles in chondrogenesis and Cartilage regeneration

“…Coding and non-coding RNAs, proteins, antigen-presenting molecules and DNA are the main compositions of exosomes. [20][21][22] Microvesicles consist of bilayer lipids containing mRNAs, miRNAs as well as lipids and cytosol. Because of their size and composition, exosomes are considered to be more important in the field of tissue engineering and regenerative medicine.…”

The effect of immune cell‐derived exosomes in the cardiac tissue repair after myocardial infarction: Molecular mechanisms and pre‐clinical evidence

“…Therefore, modulating inflammation response after MI may provide a potential approach to diminish myocardial dysfunction. Notably, there is growing evidence showing the essential role of immune cell‐derived exosomes in these functions, 15 , 16 , 17 , 18 and thus, in the present review, we aimed to summarize the immunomodulatory impacts of immune cell‐secreted exosomes on cardiac repair after MI.…”