Extracellular vesicles (EVs) are well-established mediators of cell-to-cell communication. EVs can be released by every cell type and they can be classified into three major groups according to their biogenesis, dimension, density, and predominant protein markers: exosomes, microvesicles, and apoptotic bodies. During their formation, EVs associate with specific cargo from their parental cell that can include RNAs, free fatty acids, surface receptors, and proteins. The biological function of EVs is to maintain cellular and tissue homeostasis by transferring critical biological cargos to distal or neighboring recipient cells. On the other hand, their role in intercellular communication may also contribute to the pathogenesis of several diseases, including thrombosis. More recently, their physiological and biochemical properties have suggested their use as a therapeutic tool in tissue regeneration as well as a novel option for drug delivery. In this review, we will summarize the impact of EVs released from blood and vascular cells in arterial and venous thrombosis, describing the mechanisms by which EVs affect thrombosis and their potential clinical applications.

Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity.

Reduction in brain-derived neurotrophic factor (BDNF) expression in the brain as well as mutations in BDNF gene and/or of its receptor are associated to obesity in both human and animal models. However, the association between circulating levels of BDNF and obesity is still not defined. To answer this question, we performed a meta-analysis carrying out a systematic search in electronic databases. Ten studies (307 obese patients and 236 controls) were included in the analysis. Our data show that obese patients have levels of BDNF similar to those of controls (SMD: 0.01, 95% CI: −0.28, 0.30, p = 0.94). The lack of difference was further confirmed both in studies in which BDNF levels were assessed in serum (MD: −0.93 ng/mL, 95% CI: −3.34, 1.48, p = 0.45) and in plasma (MD: 0.15 ng/mL, 95% CI: −0.09, 0.39, p = 0.23). Data evaluation has shown that some bias might affect BDNF measurements (e.g., subject recruitment, procedures of sampling, handling, and storage), leading to a difficult interpretation of the results. Standardization of the procedures is still needed to reach strong, affordable, and reliable conclusions.

Cigarette smoking engenders inflammation and endothelial dysfunction, processes implicated in atherothrombotic disease. We hypothesized that an interaction between inflammatory cytokines in smokers' blood and circulating components of cigarette smoke is necessary to induce reactive oxygen species (ROS) and cyclooxygenase-2 (COX-2) in endothelium. We then explored the molecular mechanisms involved in these effects. Serum from nine healthy active smokers (AS) compared with serum from nine non-smokers (NS) showed higher levels of interleukin-1beta (IL-1β) and tumour necrosis factor-alpha (TNF-α) and a greater ability to induce ROS production, p47phox translocation to the plasma membrane, and COX-2 mRNA and protein expression in endothelial cells (ECs). Similar results were obtained in vivo and in vitro after treatment with aqueous extracts of cigarette smoke plus IL-1β and TNF-α(TS/IL-1β/TNF-α). In ECs increased ROS production and COX-2 mRNA induced by serum from AS correlated positively with their serum levels of IL-1β and TNF-α. Moreover, a positive correlation was observed between ROS generation and COX-2 mRNA. Simultaneous immuno-neutralization of IL-1β and TNF-α prevented endothelial dysfunction induced by serum from AS. Inhibitors of NADPH oxidase and/or p47phox siRNA diminished ROS production and COX-2 expression as well as phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and Akt mediated either by AS serum or by TS/IL-1β/TNF-α. Finally, direct inhibition of p38MAPK and Akt activity also abolished COX-2 expression mediated by both types of stimuli. Our results suggest a crucial role played by interactions between inflammatory cytokines and tobacco smoke in the induction of endothelial dysfunction.