@article{e9724859766d4757ad238a463705d7ae,
title = "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.",
keywords = "MCC950, neointimal hyperplasia, NLRP3, restenosis, vascular inflammation",
author = "Grant, \{Angus J.\} and Nianji Yang and Moore, \{Matthew J.\} and Lam, \{Yuen Ting\} and Michael, \{Praveesuda L.\} and Chan, \{Alex H.P.\} and Miguel Santos and Jelena Rnjak-Kovacina and Tan, \{Richard P.\} and Wise, \{Steven G.\}",
note = "Funding Information: This work was supported by the National Health and Medical Research Council (APP1162969; S.G.W), funding from the Sydney Local Health District (S.G.W), and from NSW Health in the form of a NSW Cardiovascular Early‐Mid Research Grant (S.G.W and R.P.T H21/174585). R.P.T. receives funding as a National Heart Foundation Postdoctoral Fellow. S.G.W receives funding as a National Heart Foundation Future Leader Fellow. J.R.K receives funding as an ARC Future Fellow (FT210100668). The authors acknowledge the facilities as well as scientific and technical assistance at the Australian Center for Microscopy and Microanalysis, The University of Sydney. Funding Information: This work was supported by the National Health and Medical Research Council (APP1162969; S.G.W), funding from the Sydney Local Health District (S.G.W), and from NSW Health in the form of a NSW Cardiovascular Early-Mid Research Grant (S.G.W and R.P.T H21/174585). R.P.T. receives funding as a National Heart Foundation Postdoctoral Fellow. S.G.W receives funding as a National Heart Foundation Future Leader Fellow. J.R.K receives funding as an ARC Future Fellow (FT210100668). The authors acknowledge the facilities as well as scientific and technical assistance at the Australian Center for Microscopy and Microanalysis, The University of Sydney. Open access publishing facilitated by The University of Sydney, as part of the Wiley - The University of Sydney agreement via the Council of Australian University Librarians. Publisher Copyright: {\textcopyright} 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.",
year = "2023",
month = jul,
day = "18",
doi = "10.1002/advs.202300521",
language = "English",
volume = "10",
journal = "Advanced Science",
issn = "2198-3844",
publisher = "Wiley-VCH Verlag GmbH \& Co. KGaA",
number = "20",
}
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