Platelet-Derived Exosomes in Atherosclerosis

Abstract

Atherosclerosis (AS), the main cause of many cardiovascular diseases (CVDs), is a progressive inflammatory disease characterized by the accumulation of lipids, fibrous elements, and calcification in the innermost layers of arteries. The result is the thickening and clogging of these vessel walls. Several cell types are directly involved in the pathological progression of AS. Among them, platelets represent the link between AS, inflammation, and thrombosis. Indeed, besides their pivotal role in hemostasis and thrombosis, platelets are key mediators of inflammation at injury sites, where they act by regulating the function of other blood and vascular cell types, including endothelial cells (ECs), leukocytes, and vascular smooth muscle cells (VSMCs). In recent years, increasing evidence has pointed to a central role of platelet-derived extracellular vesicles (P-EVs) in the modulation of AS pathogenesis. However, while the role of platelet-derived microparticles (P-MPs) has been significantly investigated in recent years, the same cannot be said for platelet-derived exosomes (P-EXOs). For this reason, this reviews aims at summarizing the isolation methods and biological characteristics of P-EXOs, and at discussing their involvement in intercellular communication in the pathogenesis of AS. Evidence showing how P-EXOs and their cargo can be used as biomarkers for AS is also presented in this review.

Keywords: atherosclerosis; biomarkers; cardiovascular diseases; miRNAs; platelet-derived exosomes; platelets.

Figure 1

Role of platelets in the development and progression of AS. Platelets influence the atherosclerotic process by communicating with (a) endothelial cells (ECs), (b) leukocytes (mainly monocytes, but also neutrophils, T lymphocytes, and dendritic cells), (c) vascular smooth muscle cells (VSMCs), and (d) low-density lipoprotein (LDL), either in the native or oxidized form (ox-LDL). Collectively, these interactions induce platelets to release a variety of inflammatory mediators capable of affecting several biological functions of their target cells, including secretion, adhesion, migration, recruitment of other cell types, proteolysis, and coagulation. In the light grey boxes, the molecules participating in initial interactions between cells are indicated, with the colors representing the cells in which they are expressed. PSLG-1, P-selectin glycoprotein ligand-1; GPIbα, glycoprotein Ibα; TF, tissue factor; PF4, platelet factor 4 (or CXCL-4); LOX-1, low-density lipoprotein receptor-1; ROS, reactive oxygen species.

Figure 2

Main characteristics of P-EXOs as detected by transmission electron microcopy (TEM), flow cytometry (FC), Western blot (WB), dynamic light scattering (DLS), and nanoparticle-tracking analysis (NTA).