Abstract 174: Lacking Gata2 in Endothelial Cells Induces Apoptosis During Vascular Development

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Chih-Wen Ni ◽  
Tom Smith ◽  
Nathan D Lawson
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Zinc Finger Nucleases ◽  
Positive Staining ◽  
Vascular Endothelial ◽  
Apoptotic Protein ◽  
Flow Circulation ◽  
Media Layer

Gata2 is a transcription factor implicated in hematopoietic development. Previously, we utilized zinc-finger nucleases to generate a zebrafish mutant in gata2a, which reveals a novel role for this gene in vascular development. In particular, gata2a mutant embryos exhibit defects in blood flow circulation due to the formation of shunts within trunk blood vessels, although artery and vein identity appears normal. Here, we show that endothelial cells in gata2a mutant embryos specifically undergo apoptosis as revealed by positive staining of activated caspase-3 at 30hpf but not 24hpf. This endothelial apoptosis can be rescued by re-constitution of gata2a or overexpression of a well-known anti-apoptotic protein, bcl2l1. Interestingly, knocking-down p53 has no effect on the rescue of apoptosis in gata2a mutants, suggesting a p53 independent pathway of apoptosis. Furthermore, we find that mouse retinal vascular endothelial cells lacking gata2 also appear to undergo apoptosis, which prevent angiogenic sprouting from the superficial to media layer of retina vasculature. These findings reveal a new role of gata2 in vascular development whereby gata2 retains an anti-apoptotic function in endothelial cells.

scholarly journals Emerging Role of AP-1 Transcription Factor JunB in Angiogenesis and Vascular Development

2021 ◽  
Vol 22 (6) ◽  
pp. 2804
Author(s):  
Yasuo Yoshitomi ◽  
Takayuki Ikeda ◽  
Hidehito Saito-Takatsuji ◽  
Hideto Yonekura
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Blood Vessel ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Blood Vessel Formation ◽  
Vessel Formation

Blood vessels are essential for the formation and maintenance of almost all functional tissues. They play fundamental roles in the supply of oxygen and nutrition, as well as development and morphogenesis. Vascular endothelial cells are the main factor in blood vessel formation. Recently, research findings showed heterogeneity in vascular endothelial cells in different tissue/organs. Endothelial cells alter their gene expressions depending on their cell fate or angiogenic states of vascular development in normal and pathological processes. Studies on gene regulation in endothelial cells demonstrated that the activator protein 1 (AP-1) transcription factors are implicated in angiogenesis and vascular development. In particular, it has been revealed that JunB (a member of the AP-1 transcription factor family) is transiently induced in endothelial cells at the angiogenic frontier and controls them on tip cells specification during vascular development. Moreover, JunB plays a role in tissue-specific vascular maturation processes during neurovascular interaction in mouse embryonic skin and retina vasculatures. Thus, JunB appears to be a new angiogenic factor that induces endothelial cell migration and sprouting particularly in neurovascular interaction during vascular development. In this review, we discuss the recently identified role of JunB in endothelial cells and blood vessel formation.

scholarly journals Dual Role of Jam3b in Early Hematopoietic and Vascular Development

2019 ◽  
Author(s):  
Isao Kobayashi ◽  
Jingjing Kobayashi-Sun ◽  
Yuto Hirakawa ◽  
Madoka Ouchi ◽  
Koyuki Yasuda ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Signaling Cascade ◽  
Vascular Endothelial ◽  
Lateral Plate ◽  
Hematopoietic Stem

AbstractIn order to efficiently derive hematopoietic stem cells (HSCs) from pluripotent precursors, it is crucial to understand how mesodermal cells acquire hematopoietic or endothelial identity due to their close developmental connection. Although Npas4 has been recently identified as a conserved master regulator of hemato-vascular development, the molecular mechanisms underlying the cell fate divergence between hematopoietic and vascular endothelial cells are still unclear. Here, we show in zebrafish that the divergence of hematopoietic and vascular endothelial cells in mesodermal cells is regulated by Junctional adhesion molecule 3b (Jam3b) via two independent signaling pathways. Mutation of jam3b led to the reduction of npas4l expression in the posterior lateral plate mesoderm and defect of both hematopoietic and vascular development. Mechanistically, we uncover that Jam3b promotes endothelial specification by regulating npas4l expression through the repression of the Rap1a-Erk signaling cascade. Jam3b subsequently promotes hematopoietic development including HSCs by regulating lrrc15 expression in endothelial precursors through the activation of an integrin-dependent signaling cascade. Our data provide insight into the divergent mechanisms for instructing hematopoietic or vascular fates from mesodermal cells.

scholarly journals Shear stress augments mitochondrial ATP generation that triggers ATP release and Ca2+ signaling in vascular endothelial cells

2018 ◽  
Vol 315 (5) ◽  
pp. H1477-H1485 ◽  
Author(s):  
Kimiko Yamamoto ◽  
Hiromi Imamura ◽  
Joji Ando
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Vascular Endothelial Cells ◽  
Critical Role ◽  
Atp Release ◽  
Vascular Endothelial ◽  
The Novel ◽  
Caveolin 1 ◽  
Atp Generation

Vascular endothelial cells (ECs) sense and transduce hemodynamic shear stress into intracellular biochemical signals, and Ca2+ signaling plays a critical role in this mechanotransduction, i.e., ECs release ATP in the caveolae in response to shear stress and, in turn, the released ATP activates P2 purinoceptors, which results in an influx into the cells of extracellular Ca2+. However, the mechanism by which the shear stress evokes ATP release remains unclear. Here, we demonstrated that cellular mitochondria play a critical role in this process. Cultured human pulmonary artery ECs were exposed to controlled levels of shear stress in a flow-loading device, and changes in the mitochondrial ATP levels were examined by real-time imaging using a fluorescence resonance energy transfer-based ATP biosensor. Immediately upon exposure of the cells to flow, mitochondrial ATP levels increased, which was both reversible and dependent on the intensity of shear stress. Inhibitors of the mitochondrial electron transport chain and ATP synthase as well as knockdown of caveolin-1, a major structural protein of the caveolae, abolished the shear stress-induced mitochondrial ATP generation, resulting in the loss of ATP release and influx of Ca2+ into the cells. These results suggest the novel role of mitochondria in transducing shear stress into ATP generation: ATP generation leads to ATP release in the caveolae, triggering purinergic Ca2+ signaling. Thus, exposure of ECs to shear stress seems to activate mitochondrial ATP generation through caveola- or caveolin-1-mediated mechanisms. NEW & NOTEWORTHY The mechanism of how vascular endothelial cells sense shear stress generated by blood flow and transduce it into functional responses remains unclear. Real-time imaging of mitochondrial ATP demonstrated the novel role of endothelial mitochondria as mechanosignaling organelles that are able to transduce shear stress into ATP generation, triggering ATP release and purinoceptor-mediated Ca2+ signaling within the cells.

scholarly journals Human vascular adhesion protein 1 (VAP-1) is a unique sialoglycoprotein that mediates carbohydrate-dependent binding of lymphocytes to endothelial cells.

1996 ◽  
Vol 183 (2) ◽  
pp. 569-579 ◽  
Author(s):  
M Salmi ◽  
S Jalkanen
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Lymphoid Tissues ◽  
Vascular Endothelial ◽  
Adhesion Protein ◽  
Culture Model ◽  
Vascular Adhesion ◽  
Vascular Adhesion Protein 1

The regulated interactions of leukocytes with vascular endothelial cells are crucial in controlling leukocyte traffic between blood and tissues. Vascular adhesion protein-1 (VAP-1) is a novel, human endothelial cell molecule that mediates tissue-selective lymphocyte binding. Two species (90 and 170 kD) of VAP-1 exist in lymphoid tissues. Glycosidase digestions revealed that the mature 170-kD form of VAP-1 expressed on the lumenal surfaces of vessels is a heavily sialylated glycoprotein. The sialic acids are indispensable for the function of VAP-1, since the desialylated form of VAP-1 no longer mediates lymphocyte binding. We also show that L-selectin is not required for binding of activated lymphocytes to VAP-1 under conditions of shear stress. The 90-kD form of VAP-1 was only seen in an organ culture model, and may represent a monomeric or proteolytic form of the larger species. These data indicate that L-selectin negative lymphocytes can bind to tonsillar venules via the VAP- 1-mediated pathway. Moreover, our findings extend the role of carbohydrate-mediated binding in lymphocyte-endothelial cell interactions beyond the known selectins. In conclusion, VAP-1 naturally exists as a 170-kD sialoglycoprotein that uses sialic acid residues to interact with its counter-receptors on lymphocytes under nonstatic conditions.

Role of p38 MAPK in ICAM-1 Expression of Vascular Endothelial Cells Induced by Lipopolysaccharide

Shock ◽  
2002 ◽  
Vol 17 (5) ◽  
pp. 433-438 ◽  
Author(s):  
Wensheng Yan ◽  
Keseng Zhao ◽  
Yong Jiang ◽  
Qiaobing Huang ◽  
Jingzhen Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
P38 Mapk ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial
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