Effects of Exercise on Circulating Extracellular Vesicles in Cardiovascular Disease.

The evidence that physical exercise has multiple beneficial effects and is essential to a healthy lifestyle is widely accepted for a long-time. The functional and psychological changes promoted by exercise improve clinical outcomes and prognosis in several diseases, by decreasing mortality, disease severity, and hospital admissions. Nonetheless, the mechanisms that regulate the release, uptake, and communication of several factors in response to exercise are still not well defined. In the last years, extracellular vesicles have attracted significant interest in the scientific community due to their ability to carry and deliver proteins, lipids, and miRNA to distant organs in the body, promoting a very exciting crosstalk machinery. Moreover, increasing evidence suggests that exercise can modulate the release of those factors within EVs into the circulation, mediating its systemic adaptations.In this chapter, we summarize the effects of acute and chronic exercise on the extracellular vesicle dynamics in healthy subjects and patients with cardiovascular disease. The understanding of the changes in the cargo and kinetics of extracellular vesicles in response to exercise may open new possibilities of research and encourage the development of novel therapies that mimic the effects of exercise.

A review on comparative studies addressing exosome isolation methods from body fluids.

Exosomes emerged as valuable sources of disease biomarkers and new therapeutic tools. However, extracellular vesicles isolation with exosome-like characteristics from certain biofluids is still challenging which can limit their potential use in clinical settings. While ultracentrifugation-based procedures are the gold standard for exosome isolation from cell cultures, no unique and standardized method for exosome isolation from distinct body fluids exists. The complexity, specific composition, and physical properties of each biofluid constitute a technical barrier to obtain reproducible and pure exosome preparations, demanding a detailed characterization of both exosome isolation and characterization methods. Moreover, some isolation procedures can affect downstream proteomic or RNA profiling analysis. This review compiles and discussed a set of comparative studies addressing distinct exosome isolation methods from human biofluids, including cerebrospinal fluid, plasma, serum, saliva, and urine, also focusing on body fluid specific challenges, physical properties, and other potential variation sources. This summarized information will facilitate the choice of exosome isolation methods, based on the type of biological samples available, and hopefully encourage the use of exosomes in translational and clinical research.

Toward Neuroproteomics in Biological Psychiatry: A Systems Approach Unravels Okadaic Acid-Induced Alterations in the Neuronal Phosphoproteome.

Neuroproteomics is an evolving field of postgenomic medicine, highlighting the convergence of psychiatry/neurology and proteomics, yet compared with neurogenetics, it has received little attention. This study in rat primary neuronal cultures provides an example of a neuroproteomic approach relevant to the study of psychiatric disease pathophysiology, focusing on Alzheimer's disease. In this context, okadaic acid (OA) is routinely used in experimental designs to investigate phosphorylation-mediated events. It is a potent protein phosphatase (PP) inhibitor, particularly of PP1 and PP2A. Typically, a single protein and its phosphorylation level are monitored upon OA exposure. Although useful, this can be misleading as protein phosphorylation-mediated events involve complex signaling cascades and an array of kinases, phosphatases, and substrates. Bearing in mind the involvement of multiple pathways and cascade cross talk, this study employed a systems approach to analyze OA-induced molecular responses through PP inhibition. We showed that upon OA exposure, the recovery rate of 245 phosphoproteins significantly increased, while that of 75 significantly decreased. The prominent biological processes affected included anatomical structural development, transport, cell differentiation, and signal transduction. The associated phosphointeraction networks identified nodes representing OA-responsive phosphoproteins. Many of these are key players of signaling cascades relevant to a range of pathologies. In summary, the data presented results from a neuroproteomic preclinical study offering an array of phosphoproteins as potential targets for future diagnostic and therapeutic strategies in biological psychiatry. We note, however, the nonspecificity of targeting PPs themselves and emphasize the need for future neuroproteomic approaches toward systems psychiatry.