Quantitative Proteomics Analysis Revealed the Potential Role of lncRNA Ftx in Promoting Aortic Dissection Progression

Abstract Objective: The destruction of vascular endothelial function is an important mechanism for the formation of aortic dissection. Here, we aim to investigate the role of lncRNA Ftx in the biological functions of vascular endothelial cells, as well as the key proteins it regulates, to further explore the potential regulatory role of Ftx on the function of vascular endothelial cells in the pathogenesis of aortic dissection.Experimental Design: The expression of lncRNA Ftx was measured in aortic dissection tissues（n＝12）and age- and sex-matched patients with hypertension tissues（n＝12）. Loss and Gain-of-Function cell Models was constructed using the lentivirus mediated Ftx/Sh-Ftx transfection in HUVECs. The quantitative proteomics was performed to profile the differentially expressed proteins in cell models and further defined the crucial molecules and pathways involved in the carcinogenesis process of lncRNA Ftx. Cell experiments was conducted for valuable proteins to verify the regulatory effect by Ftx.Results: The results of clinical specimen examination showed that LncRNA Ftx was significantly over-expressed in aortic dissection tissue compared with normal aortic tissue. A total of 4348 proteins were quantified by protein mass spectrometry, which are involved in various biological processes and related signaling pathways including cell proliferation, cell apoptosis, cell functional changes and cell metabolism. Interestingly,CBX1, is a protein associated with proliferation and apoptosis of vascular endothelial cells,was up-regulated in the absence of LncRNA Ftx and down-regulated in the overexpression of LncRNA Ftx, which was further verified in HUVECs. Conclusion: This study showed that the intervention of LncRNA Ftx expression in vascular endothelial cells can regulate multiple biological processes such as cell proliferation and apoptosis, thus affecting the progression of aortic dissection. In this process, LncRNA Ftx may have a negative regulation effect on CBX1. which provided a new perspective for the mechanism of gastric cancer progression, and thus identified potential therapeutic targets for gastric cancer.

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Faculty Opinions recommendation of Role of glycolytically generated ATP for CaMKII-mediated regulation of intracellular Ca2+ signaling in bovine vascular endothelial cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1091440.545902 ◽

2007 ◽

Author(s):

Geneviève Dupont

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Vascular Endothelial

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Possible role of protein phosphorylation in the mitogenic effect of high density lipoproteins on cultured vascular endothelial cells.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)57503-2 ◽

1986 ◽

Vol 261 (17) ◽

pp. 8002-8008

Author(s):

J M Darbon ◽

J F Tournier ◽

J P Tauber ◽

F Bayard

Keyword(s):

Endothelial Cells ◽

Protein Phosphorylation ◽

Vascular Endothelial Cells ◽

High Density ◽

High Density Lipoproteins ◽

Vascular Endothelial ◽

Mitogenic Effect

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

International Journal of Molecular Sciences ◽

10.3390/ijms22062804 ◽

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.

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00204.2018 ◽

2018 ◽

Vol 315 (5) ◽

pp. H1477-H1485 ◽

Cited By ~ 15

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.

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Antigen Presentation by Vascular Endothelial Cells and Epidermal Langerhans Cells: The Role of HLA-DR

Immunological Reviews ◽

10.1111/j.1600-065x.1982.tb00434.x ◽

1982 ◽

Vol 66 (1) ◽

pp. 57-77 ◽

Cited By ~ 129

Author(s):

Henry Hirschberg ◽

Lasse R. Braathen ◽

Erik Thorsby

Keyword(s):

Endothelial Cells ◽

Antigen Presentation ◽

Langerhans Cells ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Hla Dr ◽

Epidermal Langerhans Cells

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

Journal of Experimental Medicine ◽

10.1084/jem.183.2.569 ◽

1996 ◽

Vol 183 (2) ◽

pp. 569-579 ◽

Cited By ~ 82

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.

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