Cardiovascular diseases (CVDs) continue to represent the number one cause of death and disability in industrialized countries. to replace the damaged tissue. Stem cells (SCs) have been proposed as a viable therapy option in these cases. However, despite the great enthusiasm at the beginning of the SC era, justified by promising initial results, this therapy has failed to demonstrate a significant benefit in large clinical trials. One interesting finding of SC studies is that exosomes released by mesenchymal SCs (MSCs) are able to enhance the viability of cardiomyocytes after ischaemia/reperfusion injury, suggesting that PD 0332991 HCl distributor the beneficial effects of MSCs PD 0332991 HCl distributor in the recovery of functional myocardium could be related to their capacity to secrete exosomes. Ten years ago, it was discovered that exosomes have the unique property of transferring miRNA between cells, acting as miRNA nanocarriers. Therefore, exosome-based therapy has recently been proposed as an emerging tool for cardiac regeneration as an alternative to SC therapy in the post-infarction period. This review aims to discuss the emerging role of exosomes in developing innovative therapies for cardiac regeneration as well as their potential role as candidate biomarkers or for developing new diagnostic tools. 100-1000 nm for SMV and 50-500 nm for AB), different densities (1.10-1.21 g/mL 1.16-1.28 g/mL) and cell type-specific proteins. Based on these biophysical properties, pure exosomes can be obtained using differential centrifugation with membrane filters, rate zonal centrifugation and immunoaffinity capture with magnetic beads using specific antibodies/proteins[28,29]. EMERGING ROLE OF EXOSOMES IN CVD It has been demonstrated that exosomes have beneficial effects on injured hearts, protecting cardiomyocytes in both acute and chronic models of ischaemia or in acute ischaemia/reperfusion injury[11]. Their beneficial effects have been related to a significant decrease in infarct size, reduction of fibrosis and associated remodelling, stimulation of angiogenesis and alteration of immune function[11]. Exosomes like a source of biomarkers in CVD The potential of exosomes to serve mainly because reliable biomarkers for CV diseases relies on their ability to incorporate miRNAs, RNAs, proteins and lipids for numerous medical conditions. Bioinformatics tools are currently able to differentiate the composition of a large number of miRNAs. As a result, specific mRNAs/miRNAs have been found out in exosomes isolated from individuals with AMI or with atheromatous plaques. Individuals with CAD show increased levels of circulating exosomes, especially a subpopulation rich in miR-199a and miR-126, therefore showing a great potential to serve as biomarkers for CAD[30]. At the same time, elevated levels of miR-1 and miR-133 have been recognized in the serum of individuals with acute coronary syndromes and have been shown to correlate well with troponin ideals[31]. Several studies have shown increased levels of miR-1 and miR-133 in the peripheral blood circulation of individuals with various types of ACS, including unstable angina, AMI or Takotsubo cardiomyopathy[31], while individuals with troponin-positive ACS exhibited improved levels of miR-133a and miR-499[32]. However, very few studies have attempted to validate the part of exosomes as biomarkers in coronary artery disease (CAD). Cardiomyocytes produce a large number of miRNAs. From these, four types are specifically related to AMI – miRNA-1, miRNA-133a and b, miRNA-208a and miRNA-499. During AMI, these miRNAs rapidly increase in the peripheral blood up to 3000-collapse compared to healthy individuals, indicating myocardial damage. Consequently, such a panel of miRNA biomarkers can serve as reliable markers of myocardial necrosis with a higher specificity than traditional biomarkers. Furthermore, their elevation happens much earlier than the increase in troponin, therefore representing a encouraging tool for an immediate and accurate analysis of AMI. It has also been shown that in individuals with ACS, hurt cardiomyocyte-released exosomes are rich in cardiac-specific miRNAs, such as miRNA-1, mi-RNA-208 and miRNA-133. At the same time, miRNA-133 present in exosomes Rabbit polyclonal to GRB14 can serve as a reliable biomarker for myocardial damage in AMI[16]. Elevated serum levels of exosome-derived miR-208a were correlated with deterioration of the hemodynamic status, as indicated by an increase in the Killip class (class I: no evidence of PD 0332991 HCl distributor heart failure, class II: slight to moderate heart failure, with rales less half way up the lung fields, class III: pulmonary oedema, and class IV: cardiogenic shock) and reduced survival in AMI individuals[33]. Interestingly, in individuals with AMI, numerous miRNAs inside exosomes have been associated with the event of heart failure (HF) during the post-infarction period. Matsumoto et al[34] showed that exosomal-derived miRNA-192, miRNA-194 and miRNA-34a were significantly improved in individuals with AMI who developed HF and ventricular remodelling. Exosomes mainly because therapeutic tools in CVD The use of exosomes as restorative tools is based on the premise that the use of paracrine mediators of PD 0332991 HCl distributor SCs could be more.