Role of Exosomes in Cardiovascular Physiology

With the advent of high-throughput proteomics and genomics and evolving understanding of paracrine mechanisms, particularly in cancer and development, the field of exosome biology experienced a paradigm shift; particles once thought to be involved in waste management are now widely accepted as highly conserved elements in a pathway of short- and long-range communication. All examined eukaryotic cell types—including hematopoietic cells, epithelial cells, neural cells, stem cells, adipocytes, and cancer cells—secrete exosomes in culture. Canonical exosome production has been demonstrated across all taxa of Eukaryota, from single-cell amoeboid protists to fungi, plants, and animals. In vivo, exosomes can be isolated in great abundance from all body fluids, including blood, ascites, cerebrospinal fluid, saliva, milk, and even urine. These vesicles transmit a variety of signaling molecules in their payload, notably proteins, mRNA, and noncoding RNA—including, most notably, microRNAs (miRs). Furthermore, the range of these particles and their ability to transfer their molecular payloads have been described in various models of health and disease. Indeed, there is now a wealth of evidence that exosomes can mediate autocrine, paracrine, and endocrine functions. The first area of clinical translation has been in diagnostics: Exosomes isolated from blood or urine can be used as markers of disease and prognosis in cancer and perhaps also in CNS disease and heart disease. Cell therapy for the objective of tissue regeneration has helped spur a third perspective regarding the role of exosomes in cardiovascular disease: Exosomes may mediate some or all cell-triggered therapeutic effects. (read more…)

Exosomes are nanosized particles with a diameter range of 30–100 nm and are secreted by all cell types. Enriched in cholesterol, ceramide, and phosphatidylserine, these lipid bilayer particles have a lipid content different from that of the parent cell. Markers ubiquitous in most exosomes include tetraspanins (CD9, CD63, and CD81); heat shock proteins; adhesion molecules; and markers of the ESCRT (endosomal sorting complexes required for transport) pathway, including LAMP1 and TSG101.