The angiogenic response to PF exosomes described in our study appears “specific” to PF-derived exosomes because it could not be reproduced using exosomes prepared from the plasma of the same patients. Evidence from the literature suggests that peripheral plasma exosomes could elicit different cardioprotective functions.15 Alternatively, the type of patients we have studied could present with alterations in their plasma exosomes. This study was conducted on patients with aortic stenosis undergoing aortic valve replacement. These patients are afflicted by left ventricular hypertrophy. Cardiac hypertrophy is associated with complex multicellular alterations, including hypertrophy, fibrosis, and inflammation.30 These actions are brought about by cardiac and non-cardiac cells through a variety of cell-to-cell communication pathways.30 In particular, during cardiac hypertrophy, the contractile function of the myocardium must be sustained by phenotypic changes of the capillary ECs leading to angiogenesis. Previous studies identified that proangiogenic factors released by cardiac myocytes sustain the capillary density and the oxygen supply.31, 32 Our data are in line with the new paradigm that PF exosomes and their miRNAs contribute to modulating the growth of new capillary vessels, thus protecting the heart from an accelerated failure. In support of this hypothesis, we found that the PF exosomes isolated from cardiovascular patients promote angiogenesis in vitro and in vivo. However, it is also possible that compared with healthy controls, PF exosomes from AVR patients have a reduced altered proangiogenic potential. This question could not be investigated in our human studies and will need to be deferred to work on suitable animal models.