Peripheral blood AKAP7 expression as an early marker for lymphocyte-mediated post-stroke blood brain barrier disruption

O’Connell, Grant C.; Treadway, Madison B.; Petrone, Ashley B.; Tennant, Connie S.; Lucke-Wold, Noelle; Chantler, Paul D.; Barr, Taura L.

AKAP7 exhibits strong co-expression with ITGA3 in peripheral blood following stroke. In order to gain insight into the possible role of AKAP7 in the context of post stroke BBB disruption, we next performed a genome-wide correlational analysis in which the correlation coefficients between the expression levels of AKAP7 and each of the other 18,000 genes detected via microarray were calculated. Genes were then ranked based on the absolute strength of relationship between their expression levels and those of AKAP7. We theorized that genes which were strongly co-expressed with AKAP7 would likely be mechanistically related. ITGA3, which encodes a cellular adhesion molecule known as integrin alpha 3 (ITGA3), was the only gene in the dataset whose expression levels were significantly correlated with those of AKAP7 (Fig. 3A) , exhibiting a robust positive association Scientific RepoRts | 7: 1172 | DOI:10.1038/s41598-017-01178-5 ( Fig. 3B) . Furthermore, like AKAP7, early expression levels of ITAG3 at were positively associated with the development of post-stroke severe HARM in a post-hoc logistic regression analysis controlling for age, dyslipidemia, and rtPA (p = 0.045*, Odds ratio = 3.5, 95% confidence interval = 1.0-28.4). Due to the established role of ITGA3 in mediating leukocyte extravasation 19 , we hypothesized that AKAP7 may be functionally involved in ITGA3 mediated leukocyte trafficking post-stroke.