TY  - JOUR
A1  - Haack, Timm
A1  - Abdelilah-Seyfried, Salim
T1  - The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis
JF  - Development : Company of Biologists
N2  - 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.
KW  - Endocardium
KW  - Cardiac development
KW  - Hemodynamics
KW  - Bmp
KW  - Kruppel-like factor 2
KW  - Vegf
KW  - Mechanotransduction
KW  - Zebrafish
KW  - Mouse
Y1  - 2016
U6  - https://doi.org/10.1242/dev.131425
SN  - 0950-1991
SN  - 1477-9129
VL  - 143
SP  - 373
EP  - 386
PB  - Company of Biologists Limited
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - de Vinuesa, Amaya Garcia
A1  - Abdelilah-Seyfried, Salim
A1  - Knaus, Petra
A1  - Zwijsen, An
A1  - Bailly, Sabine
T1  - BMP signaling in vascular biology and dysfunction
JF  - New journal of physics : the open-access journal for physics
N2  - The vascular system is critical for developmental growth, tissue homeostasis and repair but also for tumor development. Bone morphogenetic protein (BMP) signaling has recently emerged as a fundamental pathway of the endothelium by regulating cardiovascular and lymphatic development and by being causative for several vascular dysfunctions. Two vascular disorders have been directly linked to impaired BMP signaling: pulmonary arterial hypertension and hereditary hemorrhagic telangiectasia. Endothelial BMP signaling critically depends on the cellular context, which includes among others vascular heterogeneity, exposure to flow, and the intertwining with other signaling cascades (Notch, WNT, Hippo and hypoxia). The purpose of this review is to highlight the most recent findings illustrating the clear need for reconsidering the role of BMPs in vascular biology. (C) 2015 Elsevier Ltd. All rights reserved.
KW  - Bone morphogenetic proteins (BMP)
KW  - Signaling
KW  - Vasculature
KW  - Development
KW  - Disease
Y1  - 2016
U6  - https://doi.org/10.1016/j.cytogfr.2015.12.005
SN  - 1359-6101
SN  - 1879-0305
VL  - 27
SP  - 65
EP  - 79
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Cui, Huanhuan
A1  - Schlesinger, Jenny
A1  - Schoenhals, Sophia
A1  - Toenjes, Martje
A1  - Dunkel, Ilona
A1  - Meierhofer, David
A1  - Cano, Elena
A1  - Schulz, Kerstin
A1  - Berger, Michael F.
A1  - Haack, Timm
A1  - Abdelilah-Seyfried, Salim
A1  - Bulyk, Martha L.
A1  - Sauer, Sascha
A1  - Sperling, Silke R.
T1  - Phosphorylation of the chromatin remodeling factor DPF3a induces cardiac hypertrophy through releasing HEY repressors from DNA
JF  - Nucleic acids research
N2  - DPF3 (BAF45c) is a member of the BAF chromatin remodeling complex. Two isoforms have been described, namely DPF3a and DPF3b. The latter binds to acetylated and methylated lysine residues of histones. Here, we elaborate on the role of DPF3a and describe a novel pathway of cardiac gene transcription leading to pathological cardiac hypertrophy. Upon hypertrophic stimuli, casein kinase 2 phosphorylates DPF3a at serine 348. This initiates the interaction of DPF3a with the transcriptional repressors HEY, followed by the release of HEY from the DNA. Moreover, BRG1 is bound by DPF3a, and is thus recruited to HEY genomic targets upon interaction of the two components. Consequently, the transcription of downstream targets such as NPPA and GATA4 is initiated and pathological cardiac hypertrophy is established. In human, DPF3a is significantly up-regulated in hypertrophic hearts of patients with hypertrophic cardiomyopathy or aortic stenosis. Taken together, we show that activation of DPF3a upon hypertrophic stimuli switches cardiac fetal gene expression from being silenced by HEY to being activated by BRG1. Thus, we present a novel pathway for pathological cardiac hypertrophy, whose inhibition is a long-term therapeutic goal for the treatment of the course of heart failure.
Y1  - 2016
U6  - https://doi.org/10.1093/nar/gkv1244
SN  - 0305-1048
SN  - 1362-4962
VL  - 44
SP  - 2538
EP  - 2553
PB  - Oxford Univ. Press
CY  - Oxford
ER  -