Extracellular vesicles in cardiovascular homeostasis and disease

Abstract

Purpose of review: Extracellular vesicles have emerged as one of the most important means through which cells interact with each other and the extracellular environment, but extracellular vesicle research remains challenging due to their small size, limited amount of material required for traditional molecular biology assays and inconsistency in the methods of their isolation. The advent of new technologies and standards in the field, however, have led to increased mechanistic insight into extracellular vesicle function. Herein, the latest studies on the role of extracellular vesicles in cardiovascular physiology and disease are discussed.

Recent findings: Extracellular vesicles help control cardiovascular homeostasis and remodelling by mediating communication between cells and directing alterations in the extracellular matrix to respond to changes in the environment. The message carried from the parent cell to extracellular space can be intended for both local (within the same tissue) and distal (downstream of blood flow) targets. Pathological cargo loaded within extracellular vesicles could further result in various diseases. On the contrary, new studies indicate that injection of extracellular vesicles obtained from cultured cells into diseased tissues can promote restoration of normal tissue function.

Summary: Extracellular vesicles are an integral part of cell and tissue function, and harnessing the properties inherent to extracellular vesicles may provide a therapeutic strategy to promote tissue regeneration.

Figure 1

EVs form from direct budding of the plasma membrane or through intracellular trafficking mechanisms. Figure created using Servier Medical Art images (http://smart.servier.com).

Figure 2

EVs can transfer cargo between cells in the vascular wall, mediating local cellular cross-talk. A portion of the local EVs may also enter the bloodstream and carry transfer cargo to downstream targets. Figure created using Servier Medical Art images (http://smart.servier.com).

Figure 3

Calcific mineral forms from merger of calcifying EVs. A) Microcalcifications are observed in high resolution micro-computed tomography. Fluorescence microscopy shows microcalcifications (red) between collagen fibers (green), and electron microscopy reveals that the microcalcifications are composed of aggregated EVs. B) Collagen acts as a scaffold that directs the formation of calcification either as large calcifications beneath collagen-rich stable fibrous caps or as microcalcifications between degraded collagen fibers in vulnerable caps. Mature calcifications occur when EVs accumulate, aggregate, merge, and nucleate hydroxyapatite. Adapted from [20].