Endothelial-to-Mesenchymal Transition in Human Adipose Tissue Vasculature Alters the Particulate Secretome and Induces Endothelial Dysfunction.

OBJECTIVE: Endothelial cells (EC) in obese adipose tissue (AT) are exposed to a chronic proinflammatory environment that may induce a mesenchymal-like phenotype and altered function. The objective of this study was to establish whether endothelial-to-mesenchymal transition (EndoMT) is present in human AT in obesity and to investigate the effect of such transition on endothelial function and the endothelial particulate secretome represented by extracellular vesicles (EV). Approach and Results: We identified EndoMT in obese human AT depots by immunohistochemical co-localization of CD31 or vWF and α-SMA (alpha-smooth muscle actin). We showed that AT EC exposed in vitro to TGF-ß (tumor growth factor-ß), TNF-α (tumor necrosis factor-α), and IFN-γ (interferon-γ) undergo EndoMT with progressive loss of endothelial markers. The phenotypic change results in failure to maintain a tight barrier in culture, increased migration, and reduced angiogenesis. EndoMT also reduced mitochondrial oxidative phosphorylation and glycolytic capacity of EC. EVs produced by EC that underwent EndoMT dramatically reduced angiogenic capacity of the recipient naïve ECs without affecting their migration or proliferation. Proteomic analysis of EV produced by EC in the proinflammatory conditions showed presence of several pro-inflammatory and immune proteins along with an enrichment in angiogenic receptors. CONCLUSIONS: We demonstrated the presence of EndoMT in human AT in obesity. EndoMT in vitro resulted in production of EV that transferred some of the functional and metabolic features to recipient naïve EC. This result suggests that functional and molecular features of EC that underwent EndoMT in vivo can be disseminated in a paracrine or endocrine fashion and may induce endothelial dysfunction in distant vascular beds.

Mild exercise in female subjects impairs complex learning independent of hydration status and emotion.

INTRODUCTION: Depending on type, intensity and duration, exercise can have both beneficial and detrimental effects on cognitive function. The impact of exercise on learning and memory is also sensitive to hydration status, so we hypothesized that mild hypohydration induced with exercise, will adversely impact executive and complex memory function tasks and that these changes in cognitive function are independent of changes in emotion. METHODS: Using a cross over design, on separate days 11 women exercised on a recumbent bicycle. On day 1, women exercised to 1.5% hypohydration at 34°C, and <10% rh, on day 2, water loss from sweating was replaced by drinking water (euhydration). Pre- and post-euhydration and hypohydration, subjects underwent computer based cognitive tasks (simple, learning, memory, executive function) and visual analog testing to determine emotion. RESULTS: Exercise increased Groton Maze Learning Test errors within both conditions: [Pre: 41.5±11.8, Post: 46.8±12.4, and Pre: 41.9±9.2, Post: 46.5±12.9, hypohydrated and euhydrated, respectively, Pre vs Post, ANOVA, time effect, P=0.007], a test of acquisition, storage, and use of new knowledge. None of the measures of emotion were affected by exercise under either hydration condition. CONCLUSIONS: A bout of mild aerobic exercise compromised performance on a complex learning and memory task, but this change was unaffected by hydration status or emotion.