@misc{HaackAbdelilahSeyfried2016,
  author    = {Haack, Timm and Abdelilah-Seyfried, Salim},
  title     = {The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis},
  series = {Development : Company of Biologists},
  volume    = {143},
  journal   = {Development : Company of Biologists},
  publisher = {Company of Biologists Limited},
  address   = {Cambridge},
  issn      = {0950-1991},
  doi       = {10.1242/dev.131425},
  pages     = {373 -- 386},
  year      = {2016},
  abstract  = {Endocardial cells are cardiac endothelial cells that line the interior of the heart tube. Historically, their contribution to cardiac development has mainly been considered from a morphological perspective. However, recent studies have begun to define novel instructive roles of the endocardium, as a sensor and signal transducer of biophysical forces induced by blood flow, and as an angiocrine signalling centre that is involved in myocardial cellular morphogenesis, regeneration and reprogramming. In this Review, we discuss how the endocardium develops, how endocardial-myocardial interactions influence the developing embryonic heart, and how the dysregulation of blood flowresponsive endocardial signalling can result in pathophysiological changes.},
  language  = {en}
}
@article{FrancoObregonCambriaGreutertetal.2018,
  author    = {Franco-Obregon, Alfredo and Cambria, Elena and Greutert, Helen and Wernas, Timon and Hitzl, Wolfgang and Egli, Marcel and Sekiguchi, Miho and Boos, Norbert and Hausmann, Oliver and Ferguson, Stephen J. and Kobayashi, Hiroshi and W{\"u}rtz-Kozak, Karin},
  title     = {TRPC6 in simulated microgravity of intervertebral disc cells},
  series = {European Spine Journal},
  volume    = {27},
  journal   = {European Spine Journal},
  number    = {10},
  publisher = {Springer},
  address   = {New York},
  issn      = {0940-6719},
  doi       = {10.1007/s00586-018-5688-8},
  pages     = {2621 -- 2630},
  year      = {2018},
  abstract  = {Purpose Prolonged bed rest and microgravity in space cause intervertebral disc (IVD) degeneration. However, the underlying molecular mechanisms are not completely understood. Transient receptor potential canonical (TRPC) channels are implicated in mechanosensing of several tissues, but are poorly explored in IVDs. Methods Primary human IVD cells from surgical biopsies composed of both annulus fibrosus and nucleus pulposus (passage 1-2) were exposed to simulated microgravity and to the TRPC channel inhibitor SKF-96365 (SKF) for up to 5days. Proliferative capacity, cell cycle distribution, senescence and TRPC channel expression were analyzed. Results Both simulated microgravity and TRPC channel antagonism reduced the proliferative capacity of IVD cells and induced senescence. While significant changes in cell cycle distributions (reduction in G1 and accumulation in G2/M) were observed upon SKF treatment, the effect was small upon 3days of simulated microgravity. Finally, downregulation of TRPC6 was shown under simulated microgravity. Conclusions Simulated microgravity and TRPC channel inhibition both led to reduced proliferation and increased senescence. Furthermore, simulated microgravity reduced TRPC6 expression. IVD cell senescence and mechanotransduction may hence potentially be regulated by TRPC6 expression. This study thus reveals promising targets for future studies.},
  language  = {en}
}
@article{LisowskaRoedelManetetal.2018,
  author    = {Lisowska, Justyna and R{\"o}del, Claudia Jasmin and Manet, Sandra and Miroshnikova, Yekaterina A. and Boyault, Cyril and Planus, Emmanuelle and De Mets, Richard and Lee, Hsiao-Hui and Destaing, Olivier and Mertani, Hichem and Boulday, Gwenola and Tournier-Lasserve, Elisabeth and Balland, Martial and Abdelilah-Seyfried, Salim and Albiges-Rizo, Corinne and Faurobert, Eva},
  title     = {The CCM1-CCM2 complex controls complementary functions of ROCK1 and ROCK2 that are required for endothelial integrity},
  series = {Journal of cell science},
  volume    = {131},
  journal   = {Journal of cell science},
  number    = {15},
  publisher = {Company biologists LTD},
  address   = {Cambridge},
  issn      = {0021-9533},
  doi       = {10.1242/jcs.216093},
  pages     = {15},
  year      = {2018},
  abstract  = {Endothelial integrity relies on a mechanical crosstalk between intercellular and cell-matrix interactions. This crosstalk is compromised in hemorrhagic vascular lesions of patients carrying loss-of-function mutations in cerebral cavernous malformation (CCM) genes. RhoA/ROCK-dependent cytoskeletal remodeling is central to the disease, as it causes unbalanced cell adhesion towards increased cell-extracellular matrix adhesions and destabilized cell-cell junctions. This study reveals that CCM proteins directly orchestrate ROCK1 and ROCK2 complementary roles on the mechanics of the endothelium. CCM proteins act as a scaffold, promoting ROCK2 interactions with VE-cadherin and limiting ROCK1 kinase activity. Loss of CCM1 (also known as KRIT1) produces excessive ROCK1-dependent actin stress fibers and destabilizes intercellular junctions. Silencing of ROCK1 but not ROCK2 restores the adhesive and mechanical homeostasis of CCM1 and CCM2-depleted endothelial monolayers, and rescues the cardiovascular defects of ccm1 mutant zebrafish embryos. Conversely, knocking down Rock2 but not Rock1 in wild-type zebrafish embryos generates defects reminiscent of the ccm1 mutant phenotypes. Our study uncovers the role of the CCM1-CCM2 complex in controlling ROCK1 and ROCK2 to preserve endothelial integrity and drive heart morphogenesis. Moreover, it solely identifies the ROCK1 isoform as a potential therapeutic target for the CCM disease.},
  language  = {en}
}