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Tanshinone IIA attenuates atherosclerosis via inhibiting NLRP3 inflammasome activation
Tanshinone IIA (Tan IIA) possesses potent anti-atherogenic function, however, the underlying pharmacological mechanism remains incompletely understood. Previous studies suggest that oxidized LDL (oxLDL)-induced NLRP3 (NOD-like receptor (NLR) family, pyrin domain-containing protein 3) inflammasome ac...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835056/ https://www.ncbi.nlm.nih.gov/pubmed/33290264 http://dx.doi.org/10.18632/aging.202202 |
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author | Wen, Jiexia Chang, Yumei Huo, Shanshan Li, Wenyan Huang, Heling Gao, Yunhuan Lin, Hongyu Zhang, Jianlou Zhang, Yonghong Zuo, Yuzhu Cao, Xuebin Zhong, Fei |
author_facet | Wen, Jiexia Chang, Yumei Huo, Shanshan Li, Wenyan Huang, Heling Gao, Yunhuan Lin, Hongyu Zhang, Jianlou Zhang, Yonghong Zuo, Yuzhu Cao, Xuebin Zhong, Fei |
author_sort | Wen, Jiexia |
collection | PubMed |
description | Tanshinone IIA (Tan IIA) possesses potent anti-atherogenic function, however, the underlying pharmacological mechanism remains incompletely understood. Previous studies suggest that oxidized LDL (oxLDL)-induced NLRP3 (NOD-like receptor (NLR) family, pyrin domain-containing protein 3) inflammasome activation in macrophages plays a vital role in atherogenesis. Whether the anti-atherogenic effect of Tan IIA relies on the inhibition of the NLRP3 inflammasome has not been investigated before. In this study, we found that Tan IIA treatment of high-fat diet fed ApoE-/- mice significantly attenuated NLRP3 inflammasome activation in vivo. Consistently, Tan IIA also potently inhibited oxLDL-induced NLRP3 inflammasome activation in mouse macrophages. Mechanically, Tan IIA inhibited NF-κB activation to downregulate pro-interleukin (IL) -1β and NLRP3 expression, and decreased oxLDL-induced expression of lectin-like oxidized LDL receptor-1 (LOX-1) and cluster of differentiation 36 (CD36), thereby attenuating oxLDL cellular uptake and subsequent induction of mitochondrial and lysosomal damage — events that promote the NLRP3 inflammasome assembly. Through regulating both the inflammasome ‘priming’ and ‘activation’ steps, Tan IIA potently inhibited oxLDL-induced NLRP3 inflammasome activation, thereby ameliorating atherogenesis. |
format | Online Article Text |
id | pubmed-7835056 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-78350562021-02-03 Tanshinone IIA attenuates atherosclerosis via inhibiting NLRP3 inflammasome activation Wen, Jiexia Chang, Yumei Huo, Shanshan Li, Wenyan Huang, Heling Gao, Yunhuan Lin, Hongyu Zhang, Jianlou Zhang, Yonghong Zuo, Yuzhu Cao, Xuebin Zhong, Fei Aging (Albany NY) Research Paper Tanshinone IIA (Tan IIA) possesses potent anti-atherogenic function, however, the underlying pharmacological mechanism remains incompletely understood. Previous studies suggest that oxidized LDL (oxLDL)-induced NLRP3 (NOD-like receptor (NLR) family, pyrin domain-containing protein 3) inflammasome activation in macrophages plays a vital role in atherogenesis. Whether the anti-atherogenic effect of Tan IIA relies on the inhibition of the NLRP3 inflammasome has not been investigated before. In this study, we found that Tan IIA treatment of high-fat diet fed ApoE-/- mice significantly attenuated NLRP3 inflammasome activation in vivo. Consistently, Tan IIA also potently inhibited oxLDL-induced NLRP3 inflammasome activation in mouse macrophages. Mechanically, Tan IIA inhibited NF-κB activation to downregulate pro-interleukin (IL) -1β and NLRP3 expression, and decreased oxLDL-induced expression of lectin-like oxidized LDL receptor-1 (LOX-1) and cluster of differentiation 36 (CD36), thereby attenuating oxLDL cellular uptake and subsequent induction of mitochondrial and lysosomal damage — events that promote the NLRP3 inflammasome assembly. Through regulating both the inflammasome ‘priming’ and ‘activation’ steps, Tan IIA potently inhibited oxLDL-induced NLRP3 inflammasome activation, thereby ameliorating atherogenesis. Impact Journals 2020-11-16 /pmc/articles/PMC7835056/ /pubmed/33290264 http://dx.doi.org/10.18632/aging.202202 Text en Copyright: © 2020 Wen et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Wen, Jiexia Chang, Yumei Huo, Shanshan Li, Wenyan Huang, Heling Gao, Yunhuan Lin, Hongyu Zhang, Jianlou Zhang, Yonghong Zuo, Yuzhu Cao, Xuebin Zhong, Fei Tanshinone IIA attenuates atherosclerosis via inhibiting NLRP3 inflammasome activation |
title | Tanshinone IIA attenuates atherosclerosis via inhibiting NLRP3 inflammasome activation |
title_full | Tanshinone IIA attenuates atherosclerosis via inhibiting NLRP3 inflammasome activation |
title_fullStr | Tanshinone IIA attenuates atherosclerosis via inhibiting NLRP3 inflammasome activation |
title_full_unstemmed | Tanshinone IIA attenuates atherosclerosis via inhibiting NLRP3 inflammasome activation |
title_short | Tanshinone IIA attenuates atherosclerosis via inhibiting NLRP3 inflammasome activation |
title_sort | tanshinone iia attenuates atherosclerosis via inhibiting nlrp3 inflammasome activation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835056/ https://www.ncbi.nlm.nih.gov/pubmed/33290264 http://dx.doi.org/10.18632/aging.202202 |
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