ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 0109

Persistent Prothrombotic Activation of Platelet Pannexin 1 Channels in Antiphospholipid Syndrome

Bruna Mazetto, NaveenKumar Somanathapura, Claire Hoy, Christine Rysenga, Srilakshmi Yalavarthi, Cyrus Sarosh, Caroline Ranger, Katarina Kmetova, Jacqueline Madison, Yu Zuo and Jason Knight, University of Michigan, Ann Arbor, MI

Meeting: ACR Convergence 2023

Keywords: antiphospholipid syndrome

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Sunday, November 12, 2023

Title: (0096–0116) Antiphospholipid Syndrome Poster

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Inappropriately amplified inflammatory responses are hallmarks of many diseases, with extracellular ATP often playing a central role in the orchestration of inflammation. Regulated cellular ATP release is mainly through selective anion channels such as pannexin-1 (PANX1) channels. When cells are under stress, PANX1 channels may become constitutively opened after the cleavage of the C-terminal regions of channel subunits. While hyperactivated platelets contribute to at least a subset of antiphospholipid syndrome (APS)-associated thrombotic events, the most effective way to restrain their activation has remained elusive. Here, we aimed to evaluate the potential role of platelet PANX1 channels in the pathophysiology of APS.

Methods: Extracellular ATP release was evaluated in platelets freshly isolated from patients with positive antiphospholipid antibodies and features of APS (n=51) or from healthy controls (n=16) by standard assay kits and flow cytometry. No patients in this study had concomitant lupus. PANX1 inhibitors included carbenoxolone (CBX) and probenecid (PRB). In some experiments, platelets were stimulated with standard platelet agonists (thrombin, convulxin, and U46619) or with IgG purified from triple-positive APS patients or healthy controls. The participation of purinergic receptors in ATP-mediated platelet activation was assessed with specific inhibitors of various relevant P2X and P2Y purinergic receptors.

Results: The basal release of ATP from APS platelets was significantly higher than from healthy platelets (median 4-fold, p< 0.0001). This ATP release was strongly reduced in the presence of CBX (2-fold reduction, p< 0.05). Although the difference between APS and healthy platelets was obscured upon activation with thrombin, ATP release in this context was still prevented by either CBX (3-fold reduction, p< 0.0001) or PRB (3-fold reduction, p< 0.0001). Beyond thrombin, the PANX1 inhibitors also significantly reduced platelet ATP release in response to the thromboxane mimetic U46619 (2-fold reduction, p< 0.05). Interestingly, treatment with APS IgG was even more effective than the standard platelet agonists in opening PANX1 channels (4-fold, p< 0.0001) in just 30 minutes. This effect was completely neutralized by CBX treatment (4-fold decrease, p< 0.01). Notably, PANX1 channel-dependent ATP release was blunted by blocking either P2Y12 (p< 0.0001) or P2X7 (p< 0.0001) receptors, suggesting self-perpetuating purinergic pathways for PANX1 activation.

Conclusion: These data highlight the potential role of platelet PANX1 channels in contributing to vascular inflammation in APS by excessive extracellular ATP release. The accumulation of extracellular ATP promotes even further ATP release (and likely platelet activation) via P2Y12 and P2X7 receptors. PANX1 channel blockers such as CBX and PRB could be novel ways to restore platelet homeostasis in APS, potentially restraining thrombosis without a major impact on hemostasis (Figure 1). Experiments are now underway to further evaluate the upstream and downstream signaling partners of activated PANX1 channels in APS platelets.

Supporting image 1

Illustration of platelet PANX1 channel and downstream purinergic receptors in APS.


Disclosures: B. Mazetto: None; N. Somanathapura: None; C. Hoy: None; C. Rysenga: None; S. Yalavarthi: None; C. Sarosh: None; C. Ranger: None; K. Kmetova: None; J. Madison: None; Y. Zuo: None; J. Knight: Jazz Pharmaceuticals, 2.

To cite this abstract in AMA style:

Mazetto B, Somanathapura N, Hoy C, Rysenga C, Yalavarthi S, Sarosh C, Ranger C, Kmetova K, Madison J, Zuo Y, Knight J. Persistent Prothrombotic Activation of Platelet Pannexin 1 Channels in Antiphospholipid Syndrome [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/persistent-prothrombotic-activation-of-platelet-pannexin-1-channels-in-antiphospholipid-syndrome/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to ACR Convergence 2023

ACR Meeting Abstracts - https://acrabstracts.org/abstract/persistent-prothrombotic-activation-of-platelet-pannexin-1-channels-in-antiphospholipid-syndrome/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology