Selective NLRP3 Inflammasome Inhibitor MCC950 Suppresses Inflammation and Facilitates Healing in Vascular Materials

Abstract: Minimally invasive interventions using drug‐eluting stents or balloons are a first‐line treatment for certain occlusive cardiovascular diseases, but the major long‐term cause of failure is neointimal hyperplasia (NIH). The drugs eluted from these devices are non‐specific anti‐proliferative drugs, such as paclitaxel (PTX) or sirolimus (SMS), which do not address the underlying inflammation. MCC950 is a selective inhibitor of the NLRP3‐inflammasome, which drives sterile inflammation commonly observed in NIH. Additionally, in contrast to broad‐spectrum anti‐inflammatory drugs, MCC950 does not compromise global immune function due this selective activity. In this study, MCC950 is found to not impact the viability, integrity, or function of human coronary endothelial cells, in contrast to the non‐specific anti‐proliferative effects of PTX and SMS. Using an in vitro model of NLRP3‐mediated inflammation in murine macrophages, MCC950 reduced IL‐1β expression, which is a key driver of NIH. In an in vivo mouse model of NIH in vascular grafts, MCC950 significantly enhanced re‐endothelialization and reduced NIH compared to PTX or SMS. These findings show the effectiveness of a targeted anti‐inflammatory drug‐elution strategy with significant implications for cardiovascular device intervention.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Selective NLRP3 Inflammasome Inhibitor MCC950 Suppresses Inflammation and Facilitates Healing in Vascular Materials ; day:07 ; month:05 ; year:2023 ; extent:16
Advanced science ; (07.05.2023) (gesamt 16)

Creator
Grant, Angus J.
Yang, Nianji
Moore, Matthew J.
Lam, Yuen Ting
Michael, Praveesuda L.
Chan, Alex H.P.
Santos, Miguel
Rnjak‐Kovacina, Jelena
Tan, Richard P.
Wise, Steven G.

DOI
10.1002/advs.202300521
URN
urn:nbn:de:101:1-2023050815103648461536
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 11:01 AM CEST

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Associated

  • Grant, Angus J.
  • Yang, Nianji
  • Moore, Matthew J.
  • Lam, Yuen Ting
  • Michael, Praveesuda L.
  • Chan, Alex H.P.
  • Santos, Miguel
  • Rnjak‐Kovacina, Jelena
  • Tan, Richard P.
  • Wise, Steven G.

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