• J. Thorac. Cardiovasc. Surg. · Sep 2017

    Endothelial-specific deletion of autophagy-related 7 (ATG7) attenuates arterial thrombosis in mice.

    • Jonathan W Yau, Krishna K Singh, Yan Hou, Xi Lei, Azza Ramadan, Adrian Quan, Hwee Teoh, Wolfgang M Kuebler, Mohammed Al-Omran, Bobby Yanagawa, Heyu Ni, and Subodh Verma.
    • Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada.
    • J. Thorac. Cardiovasc. Surg. 2017 Sep 1; 154 (3): 978-988.e1.

    BackgroundThrombosis persists as a leading cause of morbidity and mortality. Given that endothelial cells (ECs) play a central role in regulating thrombosis, understanding the molecular endothelial cues that regulate susceptibility or resistance to thrombosis have important translational implications. Accordingly, we evaluated the role of endothelial autophagy in the development of thrombosis.MethodsWe generated mice in which the essential autophagy-related 7 (ATG7) gene was conditionally deleted from ECs (EC-ATG7-/- mice). Three in vivo models of thrombosis were used, and mechanistic studies were conducted with cultured human umbilical vein endothelial cells (HUVECs).ResultsWe silenced ATG7 in HUVECs and observed >60% decreases in tumor necrosis factor (TNF)-α-induced tissue factor (TF) transcript levels, protein expression, and activity. TF mRNA levels in the carotid arteries of EC-ATG7-/- mice subjected to the prothrombotic stimulus FeCl3 were lower than those in the similarly treated wild-type (WT) littermate group. Compared with WT mice, EC-ATG7-/- mice exhibited prolonged time to carotid (2-fold greater) and mesenteric (1.3-fold greater) artery occlusion following FeCl3 injury. The thrombi generated in laser-injured cremasteric arterioles were smaller in EC-ATG7-/- mice compared with WT mice, and took 2.3-fold longer to appear.ConclusionsTaken together, these results provide definitive evidence that loss of endothelial ATG7 attenuates thrombosis and reduces the expression of TF. Our findings demonstrate that endothelial ATG7, and thus autophagy, is a critical and previously unrecognized target for modulating the susceptibility to thrombosis.Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

      Pubmed     Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…