Adventitial cells are not a uniform population, and many of them have pericyte like characteristics1. Some of these cells are reported to migrate from the adventitia into deeper vascular layers2. However, little is known about the specific activation of these cells during remodelling processes and the control of cell migration through the vascular wall towards the intima. We recently identified connexin Cx43 as a modifier of cell migration3 and a closer characterisation of vascular pericytes from skeletal muscle showed a distinct expression of Cx434. The expression of connexins seems to be highly plastic and has been shown to depend decisively on the integrin expression of cells and the composition of their ECM, which is known to change in vascular inflammation.
Hypothesis: We therefore hypothesise that connexins could play a significant role in the control of activation and migration of pericyte-like cells and thereby may be an important target for therapy of pathologic remodelling processes.
Objectives: 1. To study connexin dependent migration behaviour in transmigration assays and through the wall of cultured vessels. 2. To study adventitial cell populations in vivo with special reference to pericytic characteristics, connexin and integrin expression, matrix composition and migration by intravital microscopy and immunohistochemistry at defined points of the vascular remodelling process.
Training: The ESR will be trained to use an in vivo model of intima hyperplasia by perivascular collars as well as the hindlimb ischemia model in mice. Isolated and long term cultivated mouse and hamster vessels with and without preserved adventitial layers will serve as complementary in vitro models. The ESR will learn to use Pdgfrβ+/− mice as a model of slowly developing pericyte deprivation. Studies on ECM composition of vessels and conditioning by matrices will be performed in cooperation with partner WWU, integrins with partner UF.
1 Corselli M Stem Cells Dev. 2012;21(8):1299-308. 2 Si Y Arterioscler Thromb Vasc Biol. 2012;32(4):943-54. 3 Behrens J. Eur J Cell Biol. 2010;89(11):828-38. 4 Mogensen C Acta Physiol (Oxf). 2011;201(4):413-26.
Schneider, H., Schubert, K.M., Blodow, S., Kreutz, C.P., Erdogmus, S., Wiedenmann, M., Qiu, J., Fey, T., Ruth, P., Lubomirov, L.T., Pfitzer, G., Mederos, Y., Schnitzler, M., Hardie, D.G., Gundermann, T., & Pohl, U. (2015). AMPK Dilates Resistance Arteries via Activation of SERCA and BKCa Channels in Smooth Muscle. Hypertension, 66, 108-116.
Kirsch, J., Schneider, H., Pagel, J.I., Rehberg, M., Singer, M., Hellfritsch, J., Chillo, O., Schubert, K.M., Qiu, J., Pogoda, K., Kameritsch, P., Uhl, B., Pircher, J., Deindl, E., Müller, S., Kirchner, T., Pohl, U., Conrad, M., & Beck, H. (2016). Endothelial Dysfunction, and A Prothrombotic, Proinflammatory Phenotype Is Caused by Loss of Mitochondrial Thioredoxin Reductase in Endothelium. Arterioscler Thromb Vasc Biol., 36, 1891-1899.
Ph.D student / post-doc
Prof. Ulrich Pohl