The aim of the study was to determine the effects of exercise training on improving the thoracic perivascular adipose tissue (tPVAT) phenotype (inflammation, oxidative stress, and proteasome function) in metabolic syndrome and its subsequent actions on aortic function. Methods Lean and obese (model of metabolic syndrome) Zucker rats (n=8/group) underwent 8-weeks of control conditions or treadmill exercise (70% of max speed, 1 h/day, 5 days/week). At the end of the intervention, the tPVAT was removed and conditioned media was made. The cleaned aorta was attached to a force transducer to assess endothelium-dependent and independent dilation in the presence or absence of tPVAT-conditioned media. tPVAT gene expression, inflammatory /oxidative phenotype, and proteasome function were assessed. Results The main findings were that Ex induced: (1) a beige-like, anti-inflammatory tPVAT phenotype; (2) a greater abundance of • NO in tPVAT; (3) a reduction in tPVAT oxidant production; and (4) an improved tPVAT proteasome function. Regarding aortic function, endothelium-dependent dilation was greater in exercised lean and obese groups vs. controls (p < 0.05). Lean control tPVAT improved aortic relaxation, whereas obese control tPVAT decreased aortic relaxation. In contrast, the obese Ex-tPVAT increased aortic dilation, whereas the lean Ex-tPVAT did not affect aortic dilation. Conclusion Overall, exercise had the most dramatic impact on the obese tPVAT reflecting a change towards an environment with less oxidant load, less inflammation and improved proteasome function. Such beneficial changes to the tPVAT micro-environment with exercise likely played a significant role in mediating the improvement in aortic function in metabolic syndrome following 8 weeks of exercise.

Post-stroke inflammation has been linked to poor stroke outcomes. The vascular endothelium senses and responds to circulating factors, in particular inflammatory cytokines. Although stroke associated local cerebrovascular dysfunction is well reported, the effects of a stroke on conduit artery function are not fully understood. We tested the hypothesis that stroke patients’ serum triggers leukocyte-dependent aortic endothelial dysfunction that is associated with elevated cytokines levels. Total leukocytes were isolated from healthy individuals and cells were incubated in control and stroke patients’ serum for 6 h. The quantity of cytokines in media was determined using an immunoassay. Vascular reactivity was determined by the rat aortic rings that were co-cultured with/without leukocytes and stimulated with control and stroke patient serum samples. Endothelial-dependent dilation was significantly impaired in aortic rings co-cultured with leukocytes plus stroke patients’ serum (50 ± 30% vs. 85 ± 13%, p < 0.05) vs. control patients’ serum. On the other hand, no difference was observed in aortic function stimulated with control and stroke serum without total leukocytes. Similarly, total leukocyte-derived cytokine levels were significantly increased in a time-dependent manner with stroke serum stimulation (p < 0.05). These observations support the concept that the increased response of leukocytes drives the development of stroke associated vascular endothelial dysfunction. As such, pharmacologically targeting the source of inflammatory cytokines may alleviate stroke associated peripheral vascular dysfunction.