Proper communication between the cells in the vascular wall is essential for vessel functions e.g. vascular tone and dilatation, but also for the maintenance of vascular homeostasis on the structural and functional level. This intercellular communication is mediated by numerous signaling molecules e.g. nitric oxide, but also molecules that cannot penetrate the cell membrane like cytokines and hormones, which thus, must act through membrane-bound receptors, among them ion-channels. Within the cell, these signals are relayed by a multiplicity of pathways, many of which culminate/are integrated on the level of transcription factors leading to adaptive or maladaptive outputs. The endothelial cell (EC) layer is critical to vascular homeostasis, which is underscored by the fact that endothelial dysfunction is a hallmark of all major cardiovascular diseases.
Therefore, this collaborative research project between the Sonkusare laboratory, University of Charlottesville, Virginia, USA and the Altschmied group will provide novel insights into regulatory networks in the vasculature under normal and disease conditions. By studying the cross-talk of membrane-associated signaling elements and effectors on the transcriptional level we will determine how physiological and pathological stimuli modify vascular function through these signaling circuits. The specific, complementary expertise of the partnering laboratories will allow us to pursue experimental approaches that could not be followed by the two laboratories separately.
- Gonnissen, S.*, Ptok, J., Goy, C.*, Jander, K., Jakobs, P., Eckermann, O., Kaisers, W., von Ameln, F., Timm, J., Ale-Agha, N., Haendeler, J.**, Schaal, H.**, and Altschmied, J.** (2019) High Concentration of Low-Density Lipoprotein Results in Disturbances in Mitochondrial Transcription and Functionality in Endothelial Cells. Oxid Med Cell Longev 2019, 7976382.
- Kohlgrüber, S.*, Upadhye, A.*, Dyballa-Rukes, N., McNamara, C.A., Altschmied, J. (2017) Regulation of transcription factors by reactive oxygen species and nitric oxide in vascular physiology and pathology. Antioxid Redox Signal 26, 679-699.
- Eckers, S*, Jakob, S., Heiss, C., Haarmann-Stemmann, T., Goy, C., Brinkmann, V., Cortese-Krott, M.M., Sansone, R., Esser, C., Ale-Agha, N., Altschmied, J., Ventura, N., Haendeler, J. (2016) The aryl hydrocarbon receptor promotes aging phenotypes across species. Sci Rep 6, 19618.
- Farrokh, S.*, Brillen, A.-L.*, Haendeler, J., Altschmied, J.#, Schaal, H.# (2015) Critical regulators of endothelial cell functions: for a change being alternative. Antioxid Redox Signal. 22, 1212-1229.
- Haendeler, J.*#, Mlynek, A.#, Büchner, N.#, Lukosz, M., Graf, M., Güttler, C., Jakob, S., Farrokh, S., Kunze, K., Goy, C., Guardiola-Serrano, F., Schaal, H., Cortese-Krott, M., Deenen, R., Köhrer, K., Winkler, C., Altschmied, J.* (2013) Two isoforms of Sister-of-Mammalian-Grainyhead have opposing functions in endothelial cells and in vivo. Arterioscler. Thromb. Vasc. Biol. 33, 1639-1646.
- Lukosz, M.*, Mlynek, A.*, Czypiorski, P., Altschmied, J., Haendeler, J. (2011) The transcription factor Grainyhead-like 3 (GRHL3) a new player in endothelial cell senescence, apoptosis and migration. Biochem. Biophys. Res.