Message in a Bottle: Endothelial Cell Regulation by Extracellular Vesicles

Abstract

Intercellular communication is a key biological mechanism that is fundamental to maintain tissue homeostasis. Extracellular vesicles (EVs) have emerged as critical regulators of cell-cell communication in both physiological and pathological conditions, due to their ability to shuttle a variety of cell constituents, such as DNA, RNA, lipids, active metabolites, cytosolic, and cell surface proteins. In particular, endothelial cells (ECs) are prominently regulated by EVs released by neighboring cell types. The discovery that cancer cell-derived EVs can control the functions of ECs has prompted the investigation of their roles in tumor angiogenesis and cancer progression. In particular, here, we discuss evidence that supports the roles of exosomes in EC regulation within the tumor microenvironment and in vascular dysfunction leading to atherosclerosis. Moreover, we survey the molecular mechanisms and exosomal cargoes that have been implicated in explanations of these regulatory effects.

Keywords: angiogenesis; atherosclerosis; cancer; diabetes; endothelial cells; exosomes; extracellular vesicles; miRNA.

Figure 1

Postulated mechanisms of exosome cell–cell communication.

Figure 2

Exosome-mediated regulation of the vasculature in cancer and in other pathologies. Tumor-derived exosomes may induce EC proliferation and migration, promoting the angiogenic process and have been shown to elicit leakiness of endothelial barriers and vascular permeability, thus, fostering cancer cell ingress into the bloodstream for metastatic dissemination. Furthermore, exosomes are released by ECs to self-regulate the same or neighboring cell population, including in the tumor microenvironment.