scholarly journals Endothelial TGF-β signaling instructs smooth muscle cell development in the cardiac outflow tract

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Giulia LM Boezio ◽  
Anabela Bensimon-Brito ◽  
Janett Piesker ◽  
Stefan Guenther ◽  
Christian SM Helker ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Outflow Tract ◽  
Aortic Aneurysms ◽  
Β Receptor ◽  
And Function ◽  
Cardiac Outflow

The development of the cardiac outflow tract (OFT), which connects the heart to the great arteries, relies on a complex crosstalk between endothelial (ECs) and smooth muscle (SMCs) cells. Defects in OFT development can lead to severe malformations, including aortic aneurysms, which are frequently associated with impaired TGF-β signaling. To better understand the role of TGF-β signaling in OFT formation, we generated zebrafish lacking the TGF-β receptor Alk5 and found a strikingly specific dilation of the OFT: alk5-/- OFTs exhibit increased EC numbers as well as extracellular matrix (ECM) and SMC disorganization. Surprisingly, endothelial-specific alk5 overexpression in alk5-/- rescues the EC, ECM, and SMC defects. Transcriptomic analyses reveal downregulation of the ECM gene fibulin-5, which when overexpressed in ECs ameliorates OFT morphology and function. These findings reveal a new requirement for endothelial TGF-β signaling in OFT morphogenesis and suggest an important role for the endothelium in the etiology of aortic malformations.

scholarly journals Endothelial TGF-β signaling instructs smooth muscle development in the cardiac outflow tract

2020 ◽  
Author(s):  
Giulia L.M. Boezio ◽  
Anabela Bensimon-Brito ◽  
Janett Piesker ◽  
Stefan Guenther ◽  
Christian S.M. Helker ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Muscle Development ◽  
Outflow Tract ◽  
Aortic Aneurysms ◽  
Type I ◽  
Β Receptor ◽  
And Function ◽  
Cardiac Outflow

SummaryThe development of the cardiac outflow tract (OFT), which connects the heart to the great arteries, relies on a complex crosstalk between endothelial (ECs) and smooth muscle (SMCs) cells. Defects in OFT development can lead to severe malformations, including aortic aneurysms, which have often been associated with impaired TGF-β signaling. To further investigate the role of TGF-β signaling in OFT formation, we generated zebrafish lacking the type I TGF-β receptor Alk5 and found a strikingly specific dilation of the OFT. alk5 mutants also exhibit increased EC numbers, extracellular matrix (ECM) and SMC disorganization. Surprisingly, endothelial-specific alk5 overexpression in alk5 mutants rescues both endothelial and SMC defects. Furthermore, modulation of the ECM gene fibulin-5, a TGF-β target, partially restores OFT morphology and function. These findings reveal a new requirement for endothelial TGF-β signaling in OFT morphogenesis and suggest an important role for the endothelium in the etiology of aortic malformations.

scholarly journals Author response: Endothelial TGF-β signaling instructs smooth muscle cell development in the cardiac outflow tract

2020 ◽  
Author(s):  
Giulia LM Boezio ◽  
Anabela Bensimon-Brito ◽  
Janett Piesker ◽  
Stefan Guenther ◽  
Christian SM Helker ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Cell Development ◽  
Outflow Tract ◽  
Author Response ◽  
Cardiac Outflow

PGI2 AND PGE1 INHIBIT SMOOTH MUSCLE CELL PROLIFERATION MITOTIC ACTIVITY AND EXTRACELLULAR MATRIX FORMATION

1987 ◽  
Author(s):  
H Sinzinger ◽  
T Zidek ◽  
P Fitscha ◽  
O Wagner ◽  
Waltraud Rogatti
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Mitotic Activity ◽  
Muscle Cell ◽  
Pathophysiological Role ◽  
Desoxycorticosterone Acetate

Earlier findings that activated smooth muscle cells (SMC) generate more PGI2 indicate a pathophysiological role of PG's in SMC-proliferation. In a rabbit experiment enhanced mitotic activity (MA) induced by ACTH or desoxycorticosterone acetate(DCS) is significantly depressed by both PGI2 and El.most effective.Similarly, a decrease in collagen and glycosamino-glycan-formation canbe noted. PGI2 is able to inhibit quite selectively liberation of platelet derived growthfactor (PDGF). PDGF itself stimulates vascular PGI2-generation,inhibiting further PGDF-relese long-1lasting intermittent alternating PGI2/PGE1 therfore be of optional effect concerning the local vascular SMC-action

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