Circulating leukocytes perpetuate stroke-induced aortic dysfunction

Abstract

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.

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