Exosomes in Cardiovascular Diseases

Mirca Marini, Lidia Ibba-Manneschi, Mirko Manetti

Among cardiac interstitial cells, the recently described telocytes (TCs) display the unique ability to build a supportive three-dimensional network formed by their very long and thin prolongations named telopodes. Cardiac TCs are increasingly regarded as pivotal regulators in intercellular signaling with multiple cell types, such as cardiomyocytes, stem/progenitor cells, microvessels, nerve endings, fibroblasts and immune cells, thus converting the cardiac stromal compartment into an integrated system that may drive either heart development or maintenance of cardiac homeostasis in post-natal life. Besides direct intercellular communications between TCs and neighboring cells, different types of TC-released extracellular vesicles (EVs), namely exosomes, ectosomes and multivesicular cargos, may act as shuttles for paracrine molecular signal exchange between cardiac TCs and cardiomyocytes or putative cardiomyocyte progenitors. In this review, we summarize the recent research findings on cardiac TCs and their EVs. We first provide an overview of the general features of TCs, including their peculiar morphological traits and immunophenotypes, intercellular signaling mechanisms and possible functional roles. Thereafter, we describe the distribution of TCs in normal and diseased hearts, as well as their role as intercellular communicators via the release of exosomes and other types of EVs. Finally, the involvement of cardiac TCs in cardiovascular diseases and the potential utility of TC transplantation and TC-derived exosomes in cardiac regeneration and repair are discussed.